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Objective: The aim of this study was to compare the cost and effectiveness of a minimally invasive (MI) versus traditional sternotomy (ST) approach for mitral valve surgery (MVS)., Methods: From January 1, 2003, to December 31, 2008, a total of 847 patients underwent isolated MVS at our institution. Propensity matching on 22 clinical variables was carried out to generate a study cohort of 434 patients (217 matched pairs). Direct and indirect costs from the hospital perspective were retrospectively obtained from our finance department. Total hospital costs were further stratified into 13 standardized institutional billing categories. In addition, data on morbidity, mortality, discharge location, hospital readmissions within 1 year, and freedom from reoperation were obtained., Results: Compared with ST, MIMVS was associated with a $9054 ± $3302 lower mean total hospital cost (P = .006), driven largely by a reduction in direct (P = .003) versus indirect costs (P = .06). Among the 13 billing categories, MIMVS was associated with a significant reduction in costs of cardiac imaging (P = .004), laboratory tests (P = .005), boarding and nursing (P = .001), and radiology (P = .002). More patients in the ST group required intubation for more than 72 hours (P = .019); however, there were no differences in morbidity or long-term survival (P = .334). A higher proportion of MI patients were discharged home with no nursing services (P = .018), and a higher proportion of ST patients required readmission within 1 year (P = .023). There were no differences in freedom from reoperation between groups (P = .574)., Conclusions: With equivalent efficacy across a range of measures and lower costs compared with ST, MIMVS represents a cost-saving strategy for MVS., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

In the piriform cortex, individual odorants activate a unique ensemble of neurons that are distributed without discernable spatial order. Piriform neurons receive convergent excitatory inputs from random collections of olfactory bulb glomeruli. Pyramidal cells also make extensive recurrent connections with other excitatory and inhibitory neurons. We introduced channelrhodopsin into the piriform cortex to characterize these intrinsic circuits and to examine their contribution to activity driven by afferent bulbar inputs. We demonstrated that individual pyramidal cells are sparsely interconnected by thousands of excitatory synaptic connections that extend, largely undiminished, across the piriform cortex, forming a large excitatory network that can dominate the bulbar input. Pyramidal cells also activate inhibitory interneurons that mediate strong, local feedback inhibition that scales with excitation. This recurrent network can enhance or suppress bulbar input, depending on whether the input arrives before or after the cortex is activated. This circuitry may shape the ensembles of piriform cells that encode odorant identity., (Copyright © 2011 Elsevier Inc. All rights reserved.)

Background: The purpose of this study was to determine if orthotopic heart transplantation performed within 90 days of an initial heart transplant (re-Tx) should be a contraindication to retransplantation based on inferior outcomes when compared with primary orthotopic heart transplantation recipients (control)., Methods: De-identified data were obtained from the United Network for Organ Sharing. The study population included all adult heart transplant recipients greater than 18 years old from 1995 to 2008 (n=26,804). Multivariable regression was performed in order to assess the simultaneous effect of multiple risk factors on posttransplant graft failure (PTGF) at 90 days. Secondary outcomes of interest included infection, stroke, and dialysis during the transplant hospitalization as well as primary nonfunction of the graft at 90 days., Results: Among the study cohort, there were 90 (0.34%) re-Tx patients. Median survival in this group was 1.6 years compared with 10.5 years for controls. Unadjusted PTGF, infection, dialysis, and primary nonfunction were significantly higher (p<0.001) in the re-Tx group. After risk adjustment, however, PTGF (p=0.545), infection (p=0.696), dialysis (p=0.664), stroke (p=0.115), and primary nonfunction (p=0.531), did not differ significantly between the 2 groups., Conclusions: When controlling for pretransplant recipient characteristics, retransplantation within 90 days of a previous transplant is not associated with increased morbidity or mortality. However, unadjusted overall survival was significantly worse in the re-Tx group. This suggests that although retransplantation at 90 days alone is not a risk factor for inferior outcomes, given the significant comorbidities of these patients, the indications for retransplantation within 90 days are rare and must be critically examined., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Various modifications of the Bentall procedure have been described using mechanical valve conduits. A further modification, using a bioprosthetic valve, has grown in popularity as this prevents the need for lifelong anticoagulation. Additional innovation using a stentless bioprosthetic valve has the theoretical advantages of allowing for a larger bioprosthesis and an improved durability. The technical aspects involved in designing a stentless valve conduit for use in a biological Bentall procedure are described.

Objective: Since the introduction of the cut-and-sew Cox maze procedure for atrial fibrillation, there has been substantial innovation in techniques for ablation. Use of alternative energy sources for ablation simplified the procedure and has resulted in dramatic increase in the number of patients with atrial fibrillation treated by surgical ablation. Despite its increasingly widespread adoption, there is lack of rigorous clinical evidence to establish this procedure as an effective clinical therapy., Methods: This article describes a comparative effectiveness randomized trial, supported by the Cardiothoracic Surgical Clinical Trials Network, of surgical ablation with left atrial appendage closure versus left atrial appendage closure alone in patients with persistent and long-standing persistent atrial fibrillation undergoing mitral valve surgery. Nested within this trial is a further randomized comparison of 2 different lesions sets: pulmonary vein isolation and the full maze lesion set., Results: This article addresses trial design challenges, including how best to characterize the target population, operationalize freedom from atrial fibrillation as a primary end point, account for the impact of antiarrhythmic drugs, and measure and analyze secondary end points, such as postoperative atrial fibrillation load., Conclusions: This article concludes by discussing how insights that emerge from this trial may affect surgical practice and guide future research in this area., (Copyright © 2011. Published by Mosby, Inc.)

Background: In this study we sought the following: (1) To objectively assess the risk related to various pretransplant recipient and donor characteristics; (2) to devise a preoperative risk stratification score (RSS) based on pretransplant recipient and donor characteristics predicting graft loss at 1 year; and (3) to define different risk strata based on RSS., Methods: The United Network for Organ Sharing provided de-identified patient-level data. Analysis included 11,703 orthotopic heart transplant recipients aged 18 years or greater and transplanted between January 1, 2001 and December 31, 2007. The primary outcome was 1-year graft failure. Multivariable logistic regression analysis (backward p value<0.20) was used to determine the relationship between pretransplant characteristics and 1-year graft failure. Using the odds ratio for each identified variable, an RSS was devised. The RSS strata were defined by calculating receiver operating characteristic curves and stratum specific likelihood ratios., Results: The strongest negative predictors of 1-year graft failure included the following: right ventricular assist device only, extracorporeal membrane oxygenation, renal failure, extracorporeal left ventricular assist device, total artificial heart, and advanced age. Threshold analysis identified 5 discrete RSS strata: low risk (LR, RSS: <2.55; n=3242, 27.7%), intermediate risk (IR, RSS: 2.55-5.72; n=6,347, 54.2%), moderate risk (MR, RSS: 5.73-8.13; n=1,543, 13.2%), elevated risk (ER, RSS: 8.14-9.48; n=310, 2.6%), and high risk (HR, RSS: >9.48; n=261, 2.2%). The 1-year actuarial survival (%) in the LR, IR, MR, ER, and HR groups were 93.8, 89.2, 81.3, 67.0, and 47.0, respectively., Conclusions: Pretransplant recipient variables significantly influence early and late graft failure after heart transplantation. The RSS may improve organ allocation strategies by reducing the potential negative impact of transplanting candidates who are at a high risk for poor postoperative outcomes., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Pulmonary hypertension (PH) is a serious and progressive disorder that results in right ventricular dysfunction that lead to subsequent right heart failure and death. When untreated the median survival for these patients is 2.8 years. Over the past decade advances in disease specific medical therapy considerably changed the natural history. This is reflected in a threefold decrease in the number of patients undergoing lung transplantation for PH which used to be main stay of treatment. Despite the successful development of medical therapy lung transplant still remains the gold standard for patients who fail medical therapy. Referral for lung transplant is recommended when patients have a less than 2-3 years of predicted survival or in NYHA class III or IV. Both single and bilateral lung transplants have been successfully performed for PH but outcome analyses and survival comparisons generally favor a bilateral lung transplant.

Background: The purpose of this study was to compare posttransplantation morbidity and mortality in orthotopic heart transplant recipients bridged to transplant with (1) continuous-flow left ventricular assist device (LVAD), (2) pulsatile-flow LVAD, or (3) inotropic therapy only with no LVAD., Methods: The United Network for Organ Sharing provided deidentified patient-level data. All status 1 orthotopic heart transplant recipients (n=7,744) 18 or more years of age and transplanted between January 1, 2001, and December 31, 2008, were included. Follow-up was available through June 18, 2009. Recipients were stratified into three groups: inotropes (n=5,448, 70.4%), continuous-flow LVAD (CONT [n=564, 7.3%]), and pulsatile-flow LVAD (PULS [n=1,732, 22.4%]). The primary outcome measure was risk-adjusted posttransplant graft survival (PTGS) at 90 days. Secondary outcomes included risk-adjusted PTGS at 90 days to 1 year and 1 to 5 years., Results: Unadjusted PTGS was similar in all groups (p=0.920). When compared with recipients bridged with inotropes, PTGS for patients bridged with an LVAD (CONT or PULS) did not differ in any follow-up period analyzed (<90 days, 90 days to 1 year, and 1 to 5 years). The PTGS in the CONT group (p=0.021), but not in the PULS group (p=0.244), improved significantly between the first half of the study period (2001 to 2004) and the second half (2005 to 2008)., Conclusions: Compared with recipients bridged with inotropes, neither unadjusted nor adjusted PTGS differed for either the CONT group or the PULS group. Outcomes among the CONT group improved significantly from the first to the second half of the study period., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

With the ongoing debate over health care reform in the United States, public health and policy makers have paid growing attention to the need for comparative effectiveness research (CER). Recent allocation of federal funds for CER represents a significant move toward increased evidence-based practice and better-informed allocation of constrained health care resources; however, there is also heated debate on how, or whether, CER may contribute to controlling national health care expenditures. Economic evaluation, in the form of cost-effectiveness or cost-benefit analysis, is often an aspect of CER studies, yet there are no recommendations or guidelines for providing clinical investigators with the necessary skills to collect, analyze, and interpret economic data from clinical trials or observational studies. With an emphasis on multidisciplinary research, the Clinical and Translational Science Award (CTSA) consortium and institutional CTSA sites serve as an important resource for training researchers to engage in CER. In this article, the authors discuss the potential role of CTSA sites in integrating economic evaluation methods into their comparative effectiveness education goals, using the Columbia University Medical Center CTSA as an example. By allowing current and future generations of clinical investigators to become fully engaged not only in CER but also in the economic evaluations that result from such analyses, CTSA sites can help develop the necessary foundation for advancing research to guide clinical decision making and efficient use of limited resources.

The Ross procedure or pulmonary autograft has been frequently used for surgical treatment of aortic valve disease. One considerable disadvantage of the Ross procedure is the involvement of two valves (aortic and pulmonary) in treatment of single (aortic) valve disease. Both the aortic and pulmonary valves are at risk for future degeneration. Concurrent failure of both valves after a Ross procedure is rare but presents a significant technical challenge when reoperation is necessary. We describe a novel approach to this complication using composite biological valved conduits comprised of stentless bioprosthetic valves and polyester grafts., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: The lung allocation score was initiated in May 2005 to allocate lungs on the basis of medical urgency and posttransplant survival. However, the relationship between lung allocation score and candidate outcomes remains poorly characterized. The purpose of this study was (1) to describe outcomes by lung allocation score at the time of listing and (2) to estimate the net survival benefit of transplantation by lung allocation score., Methods: The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant candidates aged 12 years or more and listed between May 4, 2005, and May 4, 2009 (n = 6082). Candidates were stratified according to lung allocation score at listing into 7 groups: lung allocation score less than 40, 40 to 49, 50 to 59, 60 to 69, 70 to 79, 80 to 89, and 90 or more. Outcomes of interest included the risk of death on the waiting list and likelihood of transplantation. The net survival benefit of transplantation was defined as actuarial median posttransplant graft survival minus actuarial median waiting list survival, where the outcome of interest was death on the waiting list or posttransplant; candidates were censored at the time of transplant or last follow-up., Results: In the lowest-priority strata (eg, <40 and 40-49), less than 4% of candidates died on the waiting list within 90 days of listing. The median net survival benefit was lowest in the lung allocation score less than 40 (-0.7 years) and lung allocation score 90+ group (1.95 years) and highest in the 50 to 59 (3.44 years), 60 to 69 (3.49 years), and 70 to 79 (2.81 years) groups., Conclusions: The mid-priority groups (eg, 50-59, 60-69, 70-79) seem to achieve the greatest survival benefit from transplantation. Although low-priority candidates comprise the majority of transplant recipients, survival benefit in this group seems to be less than in other groups given the low risk of death on the waiting list. As expected, both the time to transplant and survival on the waitlist are lower in the higher-priority strata (eg, 80-89 and 90+). However, their net survival benefit was likewise relatively low as a result of their poor posttransplant survival., (Copyright © 2011 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Over the past decade, minimally invasive cardiothoracic surgery (MICS) has grown in popularity. This growth has been driven, in part, by a desire to translate many of the observed benefits of minimal access surgery, such as decreased pain and reduced surgical trauma, to the cardiac surgical arena. Initial enthusiasm for MICS was tempered by concerns over reduced surgical exposure in highly complex operations and the potential for prolonged operative times and patient safety. With innovations in perfusion techniques, refinement of transthoracic echocardiography and the development of specialized surgical instruments and robotic technology, cardiac surgery was provided with the necessary tools to progress to less invasive approaches. However, much of the early literature on MICS focused on technical reports or small case series. The safety and feasibility of MICS have been demonstrated, yet questions remain regarding the relative efficacy of MICS over traditional sternotomy approaches. Recently, there has been a growth in the body of published literature on MICS long-term outcomes, with most reports suggesting that major cardiac operations that have traditionally been performed through a median sternotomy can be performed through a variety of minimally invasive approaches with equivalent safety and durability. In this article, we examine the technological advancements that have made MICS possible and provide an update on the major areas of cardiac surgery where MICS has demonstrated the most growth, with consideration of current and future directions.

Background: Risk stratification for mechanical circulatory support (MCS) has emerged as an important tool in patient selection and outcomes assessment. Most studies examining risk stratification have been limited to pulsatile devices. We use the Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) to stratify patients with continuous-flow devices and assess outcomes in less severe, but functionally impaired, heart failure patients., Methods: This study included 101 bridge-to-transplant and destination-therapy patients at 3 centers. Three groups were studied: Group 1, cardiogenic shock (INTERMACS Profile 1); Group 2, inotrope-dependent (INTERMACS Profile 2 or 3); and Group 3, ambulatory advanced heart failure (INTERMACS Profiles 4 to 7). The outcomes of interest were actuarial survival, survival to discharge and length of stay., Results: Survival at 36 months was better in Group 3 than in Group 1 (95.8% vs 51.1%, p = 0.011), but not between Groups 2 and 3 (68.8 vs 95.8%, p = 0.065). Lengths of stay for Groups 1 to 3 were 44, 41 and 17 days: Groups 1 vs 3, p < 0.001; Groups 2 vs 3, p < 0.001; and Groups 1 vs 2, p = 0.62. Lengths of stay for survivors were 49, 39 and 14 for the 3 groups: Groups 1 vs 3, p < 0.001; Groups 2 vs 3, p < 0.001; and Groups 1 vs 2, p = 0.28., Conclusion: INTERMACS classification is a useful metric for risk-stratifying candidates for MCS. Less acutely ill but functionally impaired heart failure patients receiving continuous-flow LVADs had longer short- and long-term survival and shorter lengths of stay compared with patients who were more acutely ill., (Copyright © 2011 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

Background: An increasing number of patients with congenital heart disease (CHD) are reaching adulthood and may require heart transplantation. The survival of these patients after listing and transplantation has not been evaluated., Methods and Results: A total of 41 849 patients (aged >18 years) were listed for primary transplantation during 1995-2009. Patients with a history of CHD (n=1035; 2.5%) were compared with those with other causes (non-CHD group) (n=40 814; 97.5%); 26 055 (62.3%) reached transplantation and were subdivided into those with (reoperation group; n=10 484; 40.2%) and without (nonreoperation group; n=15 571; 59.8%) a previous sternotomy. Survival on the waiting list was similar between groups, but mechanical ventricular assistance was not associated with superior survival to transplantation among CHD patients. CHD patients were more likely to have body mass index <18.5 at transplantation (P<0.0001), were younger, and had fewer comorbidities. Early mortality among patients with CHD was high (reoperation, 18.9% versus 9.6%; P<0.0001; nonreoperation, 16.6% versus 6.3%; P<0.0001), but by 10 years, overall survival was equivalent (53.8% versus 53.6%). Analysis was limited by the lack of specific information regarding the CHD diagnosis in most patients., Conclusions: Adults with CHD have high 30-day mortality but better late survival after heart transplantation. Mechanical circulatory assistance does not improve waiting list survival in these patients. This may be due to a combination of highly complex reoperative surgery and often poor preoperative systemic health.

Objective: The relationship between volume and outcome in many complex surgical procedures is well established., Background: No published data has examined this relationship in pediatric cardiac transplantation, but low-volume adult heart transplant programs seem to have higher early mortality., Methods: The United Network for Organ Sharing (UNOS) provided center-specific data for the 4647 transplants performed on patients younger than 19 years old, 1992 to 2007. Patients were stratified into 3 groups based on the volume of transplants performed in the previous 5 years at that center: low [<19 transplants, n = 1135 (24.4%)], medium [19–62 transplants, n = 2321(50.0%)], and high [≥63 transplants, n= 1191 (25.6%)]. A logistic regression model for postoperative mortality was developed and observed-to-expected (O:E) mortality rates calculated for each group., Results: Unadjusted long-term survival decreased with decreasing center volume (P<0.0001). Observed postoperative mortality was higher than expected at low-volume centers [O:E ratio 1.39, 95% confidence interval (CI) 1.05–1.83]. At low volume centers, high-risk patients (1.34, 0.85–2.12)--especially patients 1 year old or younger (1.60, 1.07–2.40) or those with congenital heart disease (1.36, 0.94–1.96)--did poorly, but those at high-volume centers did well (congenital heart disease: 0.90, 0.36–1.26; age<1 year: 0.75, 0.51–1.09). Similar results were obtained in the subset of patients transplanted after 1996. In multivariate logistic regression modeling, transplantation at a low-volume center was associated with an odds ratio for postoperative mortality of 1.60 (95% CI, 1.14–2.24); transplantation at a medium volume center had an odds ratio of 1.24 (95% CI, 0.92–1.66)., Conclusion: The volume of transplants performed at any one center has a significant impact on outcomes. Regionalization of care is one option for improving outcomes in pediatric cardiac transplantation.

Background: Most experts agree that primary hyperaldosteronism (PHA) caused by an aldosterone-producing adenoma (APA) is best treated by adrenalectomy. From a public health standpoint, the cost of treatment must be considered. We sought to compare the current guideline-based (surgical) strategy with universal pharmacologic management to determine the optimal strategy from a cost perspective., Methods: A decision analysis was performed using a Markov state transition model comparing the strategies for PHA treatment. Pharmacologic management for all patients with PHA was compared with a strategy of screening for and resecting an aldosterone-producing adenoma. Success rates were determined for treatment outcomes based on a literature review. Medicare reimbursement rates were calculated to estimate costs from a third-party payer perspective., Results: Screening for and resecting APAs was the least costly strategy in this model. For a reference patient with 41 remaining years of life, the discounted expected cost of the surgical strategy was $27,821. The discounted expected cost of the medical strategy was $34,691. The cost of adrenalectomy would have to increase by 156% to $22,525 from $8,784 for universal pharmacologic therapy to be less costly. Screening for APA is more costly if fewer than 9.6% of PHA patients have resectable APA., Conclusion: Resection of APAs was the least costly treatment strategy in this decision analysis model., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: Over the past decade, minimally invasive (MI) mitral valve surgery has grown in popularity. The purpose of this study was to compare both short- and long-term outcomes of mitral valve repair and replacement performed through a MI versus traditional sternotomy (ST) incision using a propensity analysis approach to account for differences in baseline risk., Methods: From January 2000 to December 2008, a total of 1,121 isolated mitral valve operations were performed at our institution (548 ST, 573 MI). Data were retrospectively collected on all patients, and a logistic regression model was created to predict selection to a MI versus ST approach. Propensity scores were then generated based on the regression model and matched pairs created using 1:1 nearest neighbor matching. There were 382 matched pairs in the analysis for a total sample size of 764, or 68.2% of the original cohort. Major outcomes of interest included cardiopulmonary bypass time, cross-clamp time, hospital length of stay, major in-hospital complications, and both short- and long-term survival., Results: Cardiopulmonary bypass time was 117.1 ± 2.0 minutes in the ST group and 139.7 ± 2.6 minutes in the MI group (p < 0.0001), and cross-clamp time was 79.6 ± 1.5 minutes in the ST group and 83.7 ± 1.9 in the MI group (p = 0.106). The average hospital length of stay was 9.81 ± 0.61 days among ST patients and 7.76 ± 0.37 days among MI patients (p = 0.0043). There was no significant difference in the frequency of major in-hospital complications between groups. The mean duration of survival follow-up was 4.2 ± 2.4 years. There was no significant difference in mortality at 30 days (p = 0.622) or 1 year (p = 0.599). In addition, there was no significant difference in long-term survival between groups (p = 0.569)., Conclusions: Although minimally invasive mitral valve surgery required a slightly longer cardiopulmonary bypass time, there was no difference in cross-clamp time, morbidity, or mortality, and hospital length of stay was significantly shorter when compared with matched sternotomy control patients., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Minimally invasive cardiac surgery has been used with increased frequency in all areas of cardiac surgery. The purpose of this study was to compare the effectiveness of a minimally invasive (MI) versus traditional sternotomy approach for the resection of cardiac masses., Methods: From January 1, 2000 to December 31, 2007, 74 patients (36 traditional sternotomy, 38 MI) underwent surgery for isolated resection of a cardiac mass. Major outcomes of interest included cardiopulmonary bypass time, cross-clamp time, conversion to full median sternotomy, final pathologic diagnosis, tumor-free margins of specimen, length of stay, major in-hospital complications (stroke, renal failure, respiratory failure, reoperation, and infection), and survival. Mean follow-up time was 4.8 years., Results: There was no significant difference in cardiopulmonary bypass time or cross-clamp time between groups. No MI cases required conversion to a full median sternotomy, and there was no evidence of new valvular insufficiency on postoperative transesophageal echocardiogram. There was also no difference between traditional sternotomy and MI groups with regard to margins of the resected specimen, nor was there a difference in the size of the resected specimen between groups. Length of stay was shorter in the MI group by 2.2 days (p = 0.044), and the proportion of strokes was also lower in the MI group (p = 0.023). There was no difference in morbidity or mortality between groups., Conclusions: A minimally invasive approach for cardiac mass resections is equally safe and effective compared with the traditional sternotomy approach. Limited surgical exposure did not compromise tumor resection margins, and the MI approach was associated with reduced hospital length of stay., (Copyright © 2010 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Previous studies have demonstrated a relationship between increasing center volume and cardiac transplant outcomes. The purpose of this study was to confirm a relationship between post-heart transplant outcomes and center experience and to determine whether this relationship persists among low- and high-risk heart transplant recipient-donor pairs., Methods and Results: The United Network for Organ Sharing (UNOS) provided deidentified patient-level data. Analysis included 8029 heart transplant recipients aged ≥18 years and transplanted between January 1, 2001 and December 31, 2006 with follow-up available through February 3, 2009. The primary outcome was observed 1-year posttransplant graft survival. Multivariable logistic regression was used to calculate expected 1-year survival for recipients. Threshold analysis identified 3 discrete risk groups of transplant recipients: high-risk, moderate-risk, and low-risk. Three discrete risk strata for center volume: low (<10.5 recipients/yr), intermediate (10.5 to 47 recipients/yr), and high (>47 recipients/yr) were also identified. χ(2) test was used to compare 1-year survival at low- and intermediate- with high-volume centers. In multivariable logistic regression analysis, annual center volume was significantly associated with posttransplant graft survival at 1 year (odds ratio [OR]=0.995, 0.992 to 0.999; P=0.010) and primary graft failure (OR=0.985, 0.972 to 0.997; P=0.015), but not stroke (OR=0.996, 0.990 to 1.003; P=0.295), infection (OR=1.001, 0.998 to 1.003; P=0.613), or dialysis (OR=1.001, 0.997 to 1.005; P=0.522). Log-rank test demonstrated significant difference in survival between volume groups with respect to high-risk (P=0.0032) and low-risk (P=0.00415), but not moderate-risk (P=0.128) patients., Conclusions: A direct relationship existed between increasing center volume and improved graft survival. Across all recipient-donor pair risk strata, posttransplant graft survival at 1 year was significantly lower at low-volume centers. The volume-outcomes relationship was strongest in the highest-risk recipient-donor category.

Objective: Most studies of anastomotic technique have been underpowered to detect subtle differences in survival. We analyzed the United Network for Organ Sharing database for trends in use and outcomes after either bicaval or traditional (biatrial) anastomoses for heart implantation., Methods: Review of United Network for Organ Sharing data identified 20,999 recipients of heart transplants from 1997 to 2007. Patients were stratified based on the technique of atrial anastomosis: standard biatrial (atrial group, n = 11,919, 59.3%), bicaval (caval group, n = 7661, 38.1%), or total orthotopic (total group, n = 519, 2.6%)., Results: The use of the bicaval anastomosis is increasing, but many transplantations continue to use a biatrial anastomosis (1997, 0.2% vs 97.6%; 2007, 62.0% vs 34.7%; P < .0001). Atrial group patients required permanent pacemaker implantation more often (odds ratio, 2.6; 95% confidence interval, 2.2-3.1). Caval group patients had a significant advantage in 30-day mortality (odds ratio, 0.83; 95% confidence interval, 0.75-0.93), and Cox regression analysis confirmed the decreased long-term survival in the atrial group (hazard ratio, 1.11; 95% confidence interval, 1.04-1.19)., Conclusions: Heart transplantations performed with bicaval anastomoses require postoperative permanent pacemaker implantation at lower frequency and have a small but significant survival advantage compared with biatrial anastomoses. We recommend that except where technical considerations require a biatrial technique, bicaval anastomoses should be performed for heart transplantation., (2010 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.)

Background: Primary graft failure (PGF) is the most common cause of short-term mortality after cardiac transplantation. The low prevalence of PGF has limited efforts at identifying risk factors for its development. The purpose of this study was to evaluate risk factors associated with PGF after heart transplantation., Methods: Deidentified data were obtained from United Network for Organ Sharing. Analysis included heart transplant recipients more than or equal to 18 years transplanted between January 1, 1999, and December 31, 2007 (n=16,716). PGF was studied from the perspective of "hard outcomes" including death or retransplantation within 90 days of transplant due to graft failure, not related to rejection or infection. Multivariate regression analysis was performed (backward, remove P>0.15) to assess the simultaneous effect of multiple variables on PGF. The odds ratio and 95% confidence interval were reported for each factor., Results: Among the 414 heart transplants complicated by PGF, 354 (85.5%) recipients died and 60 (14.5%) were retransplanted. PGF accounted for 23.4% (n=364) of all deaths (n=1555) in the first 90 days posttransplant. Categories of pretransplant variables associated with PGF included: ischemic time, donor gender, donor age, multiorgan donation, center volume, extracorporeal membrane oxygenation, mechanical circulatory support, etiology of heart failure, and reoperative heart transplant. The area under the receiver operative characteristic curve for the multivariate model was 0.764 (0.733-0.796)., Conclusions: Pretransplant recipient and donor characteristics are associated with PGF. Identification of risk factors may aid in understanding the mechanisms underlying PGF and in matching recipients with donors in efforts to diminish the high mortality associated with this complication.

Background: Over the past decade, minimally invasive cardiac surgery (MICS) has emerged as an accepted approach for the management of cardiac disease that requires a surgical solution. We report the results of an 8-year, single-institution experience with MICS., Methods: Between January 1, 2000 and December 31, 2007, a total of 910 patients underwent MICS. Major cases included aortic valve procedures (71, 7.8%), coronary artery bypass grafting (96, 10.5%), atrioseptal defect repair (103, 11.3%), and mitral valve procedures (507, 55.7%). Major outcomes of interest included the complication and mortality rates., Results: The mean age of the patients was 57 +/- 15 years; the mean ejection fraction was 55% +/- 11%; and the mean body mass index was 26.1 +/- 4.9. Overall, 782 cases (85.9%) were performed through a mini-thoracotomy. Most of the cases were accomplished through central cannulation (765, 84.0%), and venous drainage was most commonly performed in a bicaval fashion (percutaneous superior vena cava and percutaneous inferior vena cava). The mean aortic cross-clamp and cardiopulmonary bypass (CPB) times were 58.1 +/- 44.9 and 101.9 +/- 66.8 min, respectively. Conversion to full sternotomy occurred in 10 patients, and the median length of stay in hospital was 6 days. The overall complication rate was 8.8%, and the 30-day mortality rate was 2.9%. In the multivariate logistic regression analysis, risk factors associated with in-hospital complications included age, CPB time, arterial cannulation location, conversion from off-CPB to on-CPB, hepatic insufficiency, and diabetes. In the multivariate hazards regression analysis, risk factors associated with mortality included postoperative stroke, renal failure, and sternal wound infection; CPB time; and previous surgery., Conclusions: In our experience, minimally invasive approaches are effective and reproducible for a variety of cardiac operations, with acceptable operating time durations, morbidity, and mortality.

Background: The lung allocation score (LAS) was initiated in May 2005 to allocate lungs based on medical urgency and posttransplant survival. The purpose of this study was to determine if there is an association between an elevated LAS at the time of transplantation and increased postoperative morbidity and mortality., Methods: The United Network for Organ Sharing provided de-identified patient-level data. Analysis included lung transplant recipients aged >or= 12 years who received transplants between April 5, 2006, and December 31, 2007 (n = 3,836). Recipients were stratified into three groups: LAS < 50 (n = 3,161, 83.87%), LAS 50 to 75 (n = 411, 10.9%), and LAS >or= 75 (n = 197, 5.23%), referred to as low LAS (LLAS), intermediate LAS (ILAS), and high LAS (HLAS), respectively. The primary outcome was posttransplant graft survival at 1 year. Secondary outcomes included length of stay and in-hospital complications., Results: HLAS recipients had significantly worse actuarial survival at 90 days and 1 year compared with LLAS recipients. When transplant recipients were stratified by disease etiology, a trend of decreased survival with elevated LAS was observed across all major causes of lung transplant. HLAS recipients were more likely to require dialysis or to have infections compared with LLAS recipients (P < .001). In addition, length of stay was higher in the HLAS group when compared with the LLAS group (P < .001)., Conclusions: HLAS is associated with decreased survival and increased complications during the transplant hospitalization. Whereas the LAS has improved organ allocation through decreased waiting list deaths and waiting list times, lower survival and higher morbidity among HLAS recipients suggests that continued review of LAS scoring is needed to ensure optimal long-term transplant survival.

Objective: To determine the relationship between body mass index (BMI) at the time of transplant and posttransplant survival and morbidity., Summary Background Data: The recent International Society for Heart and Lung Transplantation listing criteria for heart transplantation stated that candidates should achieve a BMI <30 kg/m-or percent ideal body weight <140%-before listing for cardiac transplantation. However, data to support these recommendations are limited and often conflicting., Methods: United Network of Organ Sharing provided de-identified patient-level data. Analysis included 19,593 orthotopic heart transplant recipients aged >or=18 years and transplanted January 1 1995-December 31 2005. Follow-up data were provided through February 8, 2008. Recipients were stratified by BMI at the time of transplantation: BMI <18.5 (underweight), 18.5 to 24.99 (normal weight), 25 to 29.99 (overweight), 30 to 34.99 (obesity class I), and >or=35 (obesity class II/III). The primary outcome measure was post-transplant survival., Results: Risk-adjusted median survival in the underweight, normal weight, overweight, obesity I, and obesity II/III groups was 8.31, 10.20, 10.03, 9.51, and 9.05 years, respectively. In multivariate Cox proportional hazards regression, BMI in the overweight (HR = 1.08, 0.99-1.17; P = 0.055) and obesity I (HR = 1.05, 0.99-1.12; P = 0.091) ranges were not associated with significantly diminished survival. However, BMI in the underweight (HR = 1.26, 1.11-1.43; P < 0.001) and obesity II/III (HR = 1.18, 1.01-1.38; P = 0.030) ranges were associated with diminished posttransplant survival., Conclusion: Findings from this analysis do not suggest that obesity I (BMI of 30-34.99) is associated with significantly higher morbidity and mortality. However, underweight and obesity II/III recipients have significantly higher morbidity and mortality compared with other groups.

This study examines the effects of child abuse and domestic violence exposure in childhood on adolescent internalizing and externalizing behaviors. Data for this analysis are from the Lehigh Longitudinal Study, a prospective study of 457 youth addressing outcomes of family violence and resilience in individuals and families. Results show that child abuse, domestic violence, and both in combination (i.e., dual exposure) increase a child's risk for internalizing and externalizing outcomes in adolescence. When accounting for risk factors associated with additional stressors in the family and surrounding environment, only those children with dual exposure had an elevated risk of the tested outcomes compared to non-exposed youth. However, while there were some observable differences in the prediction of outcomes for children with dual exposure compared to those with single exposure (i.e., abuse only or exposure to domestic violence only), these difference were not statistically significant. Analyses showed that the effects of exposure for boys and girls are statistically comparable.

Background: The purpose of this study was to compare posttransplantation morbidity and mortality in orthotopic heart transplant recipients bridged to transplant with a left ventricular assist device with nonbridged recipients. To account for potential differences across device types, we stratified bridge-to-transplant recipients by type of ventricular assist device: extracorporeal (EXTRA), paracorporeal (PARA), and intracorporeal (INTRA)., Methods: The United Network for Organ Sharing provided de-identified patient-level data. The study population included 10,668 orthotopic heart transplant recipients aged 18 years old or older and undergoing transplantation between January 1, 2001, and December 31, 2006. Follow-up data were provided through August 3, 2008, with a mean follow-up time of 3.17 +/- 2.15 years (range, 0-8.11 years). The primary outcome was actuarial posttransplant graft survival. Other outcomes of interest included infection, stroke, and dialysis during the transplant hospitalization; primary graft failure at 30 days; transplant hospitalization length of stay; and long-term complications including diabetes mellitus, transplant coronary artery disease, and chronic dialysis. Multivariable Cox proportional hazards regression (backward, P < .15) was used to determine the relationship between groups and overall graft survival, and multivariable logistic regression analysis (backward, P < .15) was used to determine the relationship between groups and secondary outcome measures., Results: In multivariable Cox regression analysis, when compared with the nonbridged group, risk-adjusted greater than 90-day graft survival was diminished among the EXTRA group (hazard ratio = 3.54, 2.28-5.51, P < .001), but not the INTRA group (1.04, 0.719-1.51, P = .834) or the PARA group (1.06, 0.642-1.76, P = .809). There were no significant differences in risk-adjusted graft survival across the 4 groups during the 90-days to 1-year or 1- to 5-year intervals. However, at more than 5 years, risk-adjusted graft survival in the INTRA group (0.389, 0.205-0.738, P = .004) was better than in the nonbridged group. The EXTRA, PARA, and INTRA groups all experienced increased risks of infection. The EXTRA group had increased risks of dialysis, stroke, and primary graft failure at 30 days, whereas neither the PARA nor the INTRA group differed from the nonbridged group. Long-term complications did not differ by group., Conclusion: The use of implantable left ventricular assist devices as bridges to transplantation, including both intracorporeal and paracorporeal devices, is not associated with diminished posttransplant survival. However, 90-day survival was diminished in recipients bridged with extracorporeal devices.

Objectives: The purpose of this study was to create a preoperative risk stratification score (RSS) based on pretransplant recipient characteristics that could be used to predict mortality following lung transplantation., Methods: United Network for Organ Sharing provided de-identified patient-level data. The study population included 8780 adult recipients (age > 12 years) having lung transplantation from January 1, 1999, to December 31, 2006. Multivariate logistic regression (backward, P > .10) was performed. Using the odds ratio for each identified variable, an RSS was devised. The RSS included only pretransplant recipient variables and excluded donor variables., Results: The strongest negative predictors of 1-year survival included extracorporeal membrane oxygenation, decreased estimated glomerular filtration rate, total bilirubin >2.0 mg/dL, recipient age, hospitalization at time of transplant, O(2) dependence, cardiac index <2, steroid dependence, donor:recipient weight ratio <0.7, all non-cystic fibrosis/chronic obstructive pulmonary disease etiologies, and female donor-to-male recipient. Threshold analysis identified 4 discrete groups: low risk, moderate, elevated risk, and high risk. The 1-year actuarial survival was 80.4% for the entire group, compared with 56.8% in the high-risk group (RSS > 7.2, n = 490; 6%)., Conclusion: Pretransplant recipient variables significantly influence both early and late survival following lung transplantation. Some patients face a higher than average risk of mortality during their first year posttransplant, which challenges the goals of equitable organ allocation. RSS may improve organ allocation strategies by avoiding the potential negative impact of performing transplantation in extremely high-risk candidates.

Background: Aprotinin was the subject of recent controversy regarding adverse clinical outcomes following cardiac surgery. We compared the role of Aprotinin and epsilon-aminocaproic acid on clinical outcomes and the attenuation of the postcardiopulmonary bypass (CPB) response at the genomic expression and cytokine (protein) level., Methods: Thirty-nine low-risk patients undergoing coronary revascularization (CABG) and/or valve procedures using cardiopulmonary CPB were enrolled into a prospective cohort study. Aprotinin or epsilon-aminocaproic acid was administered to patients. Gene expression was assessed from whole blood mRNA samples collected preoperatively (PRE) and 6 hours (6H) postoperatively. Validation of gene expression was performed with SYBR Green real-time polymerase chain reaction. Cytokine values were quantified from serum preoperatively and postoperatively at 6 H and 4 days and analyzed in a blinded fashion., Results: No difference was detected in baseline characteristics. Inflammatory markers measured did not reveal significant difference between patients receiving Aprotinin (APR) and those receiving epsilon-aminocaproic acid (Amicar). Intraoperative parameters and postoperative outcomes were not significantly different. Compared with PRE samples, 6H samples had 264 upregulated and 548 downregulated genes uniquely in the APR group compared to 4826 upregulated and 1114 downregulated genes uniquely in the Amicar group (p < 0.001). Compared to patients in the Amicar group, APR patients had significantly different gene expression pathways involving NF-kappabeta regulation, programmed cell death and cell-cell adhesion. None of the patients developed postoperative stroke, myocardial infarction, or systemic infections., Conclusions: Aprotinin leads to significantly less genomic expression variability following CPB compared to Amicar and has a differential effect on specific genomic pathways.

Background: The purpose of this study is to determine the clinical outcomes associated with alternate listing transplantation, which utilizes "marginal" donor organs by transplanting them into high-risk recipients who fail to meet the standard criteria for transplantation., Methods: The United Network for Organ Sharing provided de-identified patient-level data. Analysis focused on patients undergoing heart transplantation between January 1, 1999, and December 31, 2005 (n = 13,024). High-risk criteria included age more than 65 years old, retransplantation, hepatitis C-positive, human immunodeficiency virus-positive, creatinine clearance less than 30 mL/min, diabetes mellitus with peripheral vascular disease, and diabetes with creatinine clearance less than 40 mL/min. Marginal donor criteria included age more than 55 years, diabetes mellitus, hepatitis C-positive, human immunodeficiency virus-positive, ejection fraction less than 45%, and donor:recipient weight less than 0.7., Results: Survival in the standard transplant group, defined as non-high-risk patients who received nonmarginal organs, was better than in all other groups (p < 0.001). Alternate listing transplantation patients had the worst survival (p < 0.001). The 5-year survival for the alternate listing transplantation group was 51.4%, compared with 75.1% in the standard transplant group; the standard transplant patients, with the lowest incidence of in-hospital infection (21.1%) and dialysis (7.1%), also had the best transplant hospitalization outcomes (p < 0.001). In contrast, alternate listing transplantation patients had the highest incidence of in-hospital infection (35.4%; p < 0.001). Length of stay during transplant hospitalization was also shortest in the standard transplant group (18.8 days; p < 0.001)., Conclusions: Alternate listing transplantation is associated with greater morbidity and resource utilization compared with standard transplantation. However, this strategy offers a median survival of 5.2 years to patients who would otherwise be expected to live 1 year, and therefore, may be reasonably applied to expand the benefits of transplantation. Further studies examining the costs and quality of life related to this approach are needed.

Hypothesis: Pretransplantation patient characteristics determine survival following combined heart and kidney transplantation (HKT)., Design: Time-to-event analysis., Setting: Academic research., Patients: The United Network for Organ Sharing provided deidentified patient-level data. Analysis included 19,373 heart transplant recipients from January 1, 1995, to December 31, 2005., Main Outcome Measures: Multivariate Cox proportional hazards regression analysis was performed to identify pretransplantation recipient characteristics associated with improved long-term survival following HKT. Kaplan-Meier survival functions and Cox proportional hazards regression were used for time-to-event analysis. Using the relative risks calculated in regression analysis, weights were assigned for each risk factor, allowing for the construction of a risk score., Results: Among heart transplant recipients, 264 (1.4%) underwent HKT. Factors associated with diminished survival included peripheral vascular disease, recipient age older than 65 years, nonischemic etiology of heart failure, dialysis dependence at the time of transplantation, and bridge to transplantation using a ventricular assist device. After stratification by risk score, 1-year survival was 93.2% and 61.9% in the lowest- and highest-risk HKT groups, respectively. Further stratification by estimated glomerular filtration rate (eGFR) was performed based on a previous study showing decreased survival of patients undergoing orthotopic heart transplantation with a preoperative eGFR of less than 33 mL/min. Low-risk patients with an eGFR of less than 33 mL/min undergoing HKT constituted the only group that had significantly better survival compared with isolated patients undergoing orthotopic heart transplantation with eGFRs and risk scores in the same range (P = .006)., Conclusions: When patients were stratified by risk score and by diminished eGFR (<33 mL/min), low-risk HKT recipients with a diminished eGFR had improved survival following HKT over isolated heart transplant recipients. Only low-risk patients with combined kidney failure (eGFR, <33 mL/min) and heart failure seem to gain a survival benefit from HKT.

Technological innovation--broadly defined as the development and introduction of new drugs, devices, and procedures--has played a major role in advancing the field of cardiothoracic surgery. It has generated new forms of care for patients and improved treatment options. Innovation, however, comes at a price. Total national health care expenditures now exceed $2 trillion per year in the United States and all current estimates indicate that this number will continue to rise. As we continue to seek the most innovative medical treatments for cardiovascular disease, the spiraling cost of these technologies comes to the forefront. In this article, we address 3 challenges in managing the health and economic impact of new and emerging technologies in cardiothoracic surgery: (1) challenges associated with the dynamics of technological growth itself; (2) challenges associated with methods of analysis; and (3) the ways in which value judgments and political factors shape the translation of evidence into policy. We conclude by discussing changes in the analytical, financial, and institutional realms that can improve evidence-based decision-making in cardiac surgery.

Background: In this study, we sought to confirm which types of device-related infections impact bridge-to-transplant rates. We also aimed to determine the effect of device-related infections on post-transplant survival and post-transplant infection., Methods: We retrospectively reviewed paper and electronic medical records for 149 patients undergoing left ventricular assist device (LVAD) implantation as a bridge to transplantation at the Columbia Presbyterian Medical Center between 2000 and 2006. The primary outcome measures were survival to transplantation, post-transplant infection and post-transplant survival., Results: Patients with sepsis were less likely to be successfully bridged to cardiac transplantation (7 of 22 vs 103 of 127, 31.8% vs 81.1%, p = 0.01). However, if transplanted, their survival rates at 1 year were not decreased (6 of 7 vs 85 of 103, 85.7% vs 82.5%, p = 1.00). No other pre-transplant device-related infection affected post-transplant survival at 1 year (22 of 27 vs 69 of 83, 81.5% vs 83.1%, p = 1.00). Pre-transplant drive-line infections predicted post-transplant infection in former drive-line or pocket sites (11 of 16 vs 14 of 94, 68.8% vs 14.9%, p = 0.01) and increased overall post-transplant hospital length of stay (16 vs 19 days, p = 0.04). They did not, however, affect post-transplant survival at 1 year (22 of 25 vs 69 of 85, 88% vs 81.2%, p = 0.56)., Conclusions: Although survival to transplantation was diminished in LVAD patients with sepsis, if successfully transplanted, post-transplant survival was unaffected. Patients with local device infections and signs of early sepsis may warrant evaluation for urgent transplantation. A pre-transplant drive-line infection was associated with post-transplant infection in either the former pocket or drive-line site, and increased overall length of stay, but it did not decrease post-transplant survival.

Neuronal firing is regulated by the complex interaction of multiple depolarizing and hyperpolarizing currents; intrinsic firing, which defines the neuronal ability to generate action potentials in the absence of synaptic excitation, is particularly sensitive to modulation by currents that are active below the action potential threshold. Cerebellar unipolar brush cells (UBCs) are excitatory granule layer interneurons that are capable of intrinsic firing; here we show that, in acute mouse cerebellar slices, barium-sensitive background potassium channels of UBCs effectively regulate intrinsic firing. We also demonstrate that these channels are regulated by group II metabotropic glutamate receptors (mGluRs), which we show to be present in both of the known subsets of UBCs, one of which expresses calretinin and the other mGluR1alpha. Finally, we show that background potassium currents controlling UBCs' firing are mediated by at least two channel types, one of which is sensitive and the other insensitive to the GIRK blocker tertiapin. Thus in UBCs, glutamatergic transmission appears to have a complex bimodal effect: although it increases spontaneous firing through activation of ionotropic receptors, it also has inhibitory effects through the mGluR-dependent activation of tertiapin-sensitive and -insensitive background potassium currents.

Objectives: To further our understanding of the potential protective effects of one organ allograft for another in combined organ transplants by comparing rejection-free survival and the 1-year rejection rate of each type of combined organ transplant., Summary Background Data: Liver allografts have been thought to be immunoprotective of other donor-specific allografts. Recent observations have extended this property to other organs., Methods: Analysis of data from the United Network of Organ Sharing included recipients 18 years or older (except those receiving intestinal transplants) transplanted between January 1, 1994, and October 6, 2005, and excluded those with a previous transplant (n = 45,306), live-donor transplant (n = 80,850), or insufficient follow-up (n = 4304). Patients were followed from transplant until death (n = 41,524), retransplantation (n = 4649), or last follow-up (n = 87,243)., Results: A total of 133,416 patients were analyzed. Rejection rates for allografts co-transplanted with donor-specific primary liver, kidney, and heart allografts are significantly lower than rejection rates for allografts transplanted alone. Allografts accompanying primary intestinal or pancreatic allografts did not have reduced rejection rates. A decreased rate of rejection was seen in interval kidney-heart transplants when allografts shared partial antigenic identity. Decreased rates of rejection were also seen in transplants of 2 donor-specific organs of the same type., Conclusions: In combined simultaneous transplants, heart, liver, and kidney allografts are themselves protected and protect the other organ from rejection. Analysis of interval heart-kidney allografts suggests the need for partial antigenic identity between organs for the immunoprotection to take effect. This was not demonstrated in interval liver-kidney transplants. Increased antigen load of identical antigens, as seen in double-lung and double-kidney transplants, also offers immunologic protection against rejection.

Objective: To examine patterns of resource use and the cost of care for patients with advanced heart failure treated with medical management (MM) during the final 2 years of life., Methods and Results: The study population (n=47, mean age 70.4 years+/-7.06) included patients randomized to the MM arm of the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure trial. Inpatient and outpatient use data were obtained from the clinical dataset and Centers for Medicare and Medicaid Services (beginning January 1, 1998). Cost and resource use were tracked from the date of death (t(d)) backward in 3-month intervals (eg, t(d-1), t(d-2)). In the primary analysis, costs were summed across intervals. The mean cost of MM in the final 2 years of life was $156,169, with 50.5% ($78,880.39) expended in the final 6 months. The mean quarterly cost increased (P < .01) 4.9-fold from t(d-8) ($8,816 +/- $14,270) to t(d-1) ($42,836 +/- $41,407). The number of inpatient days increased (P < .01) 6.6-fold from 3.8+/-4.7 days to 22.2+/-23.5 days during the same time intervals., Conclusion: This current economic analysis extends on previous findings by demonstrating that medical therapy in advanced and end-stage heart failure is associated with significant costs and resource consumption; these costs and resource consumption increase significantly as death approaches.

Objective: Biomaterials and textured surfaces in early pulsatile left ventricular assist devices (HeartMate I; Thoratec Corporation, Pleasanton, Calif) may increase immunologic risk through allosensitization. We hypothesized that axial-flow devices without biologic membranes or textured surfaces (HeartMate II; Thoratec; and DeBakey; MicroMed Cardiovascular, Inc, Houston, Tex) would cause less allosensitization than devices with such membranes and surfaces., Methods: HeartMate II and DeBakey (n = 24) and HeartMate I (n = 36) devices were implanted from 1999 to 2006 in patients with severe heart failure cohort-matched for age, etiology, and support duration. Serum samples reacting with more than 10% of the HLA reference panel were considered positive for anti-HLA antibodies. Endomyocardial biopsy samples were collected after transplant., Results: There were no significant cohort differences in age, etiology, sex, blood transfusion, or support duration. Anti-HLA antibodies were not detected at implantation of either HeartMate II and DeBakey or HeartMate I devices; however, significant increases in anti-HLA antibodies were present within 1 and 3 months of support with HeartMate I but not HeartMate II and DeBakey devices. Overall, fewer patients with HeartMate II and DeBakey devices demonstrated positive anti-HLA antibodies during support (8% vs 28%, P = .02), and fewer episodes of acute rejection per patient were seen within the first 9 posttransplant months(0.31 vs 0.69, P = .052). Long-term posttransplant survival was not different between groups., Conclusion: Hemodynamic support with HeartMate II and DeBakey devices produced less allosensitization than did HeartMate I devices. Device selection may improve clinical outcomes for high-risk patients.

Objectives: The use of mechanical circulatory support to bridge pediatric patients to cardiac transplantation presents unique challenges because of the difficult anatomy and physiology in these patients., Methods: The United Network for Organ Sharing provided deidentifed patient-level data. The study population included 2532 transplantations performed on patients less than 19 years old in status 1/1A/1B between 1995 and 2005. Mechanical circulatory support was used in 431 patients: 241 (9.5%) received ventricular assist devices, 171 (6.8%) underwent extracorporeal membrane oxygenation, and 19 (0.8%) received intra-aortic balloon pumps., Results: Patients supported on ventricular assist devices had similar levels of hospitalization and intensive care use and less need for inotropic support (P < .0002) than had those not needing support. Five- and 10-year posttransplantation survival was better in patients receiving ventricular assist devices and patients not receiving mechanical circulatory support than in patients receiving extracorporeal membrane oxygenation or intra-aortic balloon pumping (P < .0001). Among mechanically supported patients, patients with a body surface area of less than 0.30 (odds ratio, 1.70; 95% confidence interval, 1.18-2.43) and those requiring extracorporeal membrane oxygenation (odds ratio, 1.65; 95% confidence interval, 1.15-2.35) or intra-aortic balloon pumping (odds ratio, 1.91; 95% confidence interval, 1.02-3.56) had higher long-term mortality. The use of a ventricular assist device at transplantation did not predict higher long-term, posttransplantation mortality., Conclusions: Pediatric patients requiring a pretransplantation ventricular assist device have long-term survival similar to that of patients not receiving mechanical circulatory support. Early survival among patients undergoing extracorporeal membrane oxygenation and infants is poor, reinforcing the need for improvements in device design and physiologic management of infants and neonates.

The emergent healthcare value era, its consequences, and what drug firms need to do about it.

Objective: Studies of high-risk pediatric cardiac transplant recipients are lacking. The purpose of this study is to evaluate early posttransplant survival in high-risk pediatric patients., Methods: The United Network for Organ Sharing (UNOS) provided de-identified patient-level data. The study population included 3502 recipients aged less than 21 years who underwent transplantation from January 1, 1995, through December 31, 2005. Recipients were stratified on the basis of the presence or absence of high-risk criteria: pulmonary vascular resistance index greater than 6 Wood units/m2 (n = 285, 8.1%), creatinine clearance less than 40 mL/min (308, 8.8%), hepatitis C positivity (33, 0.9%), donor/recipient weight ratio less than 0.7 (80, 2.3%), panel reactive antibody greater than 40% (235, 6.7%), retransplantation (235, 6.7%), and age less than 1 year old (840, 24.0%)., Results: Overall, 1575 (45.0%) patients met at least one high-risk criterion. Higher numbers of high-risk criteria in a patient were correlated with increased 30-day mortality (0 high-risk criteria: 5.2%; 1 criterion: 7.9%; 2 criteria: 12.9%; and 3 or more criteria: 25.0%; P < .0001) and poor long-term survival (P < .0001). Among patients with high-risk criteria, a simplified scoring scale accurately predicts both 30-day and contingent 1-year mortality (P < .0001)., Conclusions: Individually, the effect of high-risk criteria on posttransplant survival varied; however, increasing numbers of criteria in a patient resulted in a cumulative increase in mortality. A scoring scale allows for the prediction of approximate mortality rates after transplantation. These findings suggest that recipient criteria for transplantation should focus on the number of high-risk criteria as well as clinical status, rather than the presence or absence of a single risk factor.

Objectives: To investigate the effect of epicardial fat on surgical atrial fibrillation ablation performance using an in vitro model. Two tissue models were employed to investigate standard penetration and maximal lesion depth performance of bipolar radiofrequency (RF), microwave, and laser energy sources., Methods: Ventricular veal tissue was utilized in various thicknesses (3 mm, 5 mm, 7 mm, 15 mm). Epicardial fat was modeled by layering porcine fat (1 mm, 2 mm and 4 mm) on moistened tissue. In each group, 8 to 10 lesions were created. Post ablation, tissue samples were sectioned and ablation depth of each myocardial section measured using 1% tetrazolium tetrachloride dye solution., Results: The laser energy source produced nearly 100% transmural lesions in almost all study groups irrespective of myocardium thickness and fat thickness. The microwave device maintained transmurality in all 3-mm and most 5-mm myocardium trials but fell to near zero with all 7-mm myocardium trials. The bipolar RF maintained transmurality only when no fat was applied. In the maximal lesion depth models, the laser was capable of producing lesions >8 mm with no fat and >6 mm with either 2 mm or 4 mm of fat present. The microwave produced lesions in the no fat (>6 mm) and 2-mm (>4 mm) fat group. The bipolar RF produced 83% transmurality with no fat and zero percent transmurality with 2 mm of fat present., Conclusions: Epicardial fat can severely limit transmurality in energy sources that utilize conductive heating. Laser energy was uniformly superior at producing both transmural and deep lesions irrespective of the presence of fat.

Background: The purpose of this study was to assess (1) the relationship between donor-recipient cytomegalovirus (CMV) serologic status and posttransplant survival in the current era and (2) temporal changes in posttransplant survival by CMV matching status., Methods: De-identified data were obtained from the United Network for Organ Sharing. Based on pretransplant CMV serologic status (+ or -) of recipients (R) and donors (D), posttransplant survival was compared among three groups: D+ /R-, D+/- /R+, and D- /R-. Primary analysis focused on transplants performed January 1, 2000 to December 31, 2004, in recipients 18 years of age or older. To assess temporal trends in survival among groups, all lung transplants occurring between January 1, 1990, and December 31, 2004, were considered and divided into three periods based on transplant year: 1990 through 1994, 1995 through 1999, and 2000 through 2004. The primary outcome measure was survival, reported as rate of death per 100 patient-years. Kaplan-Meier analysis with log-rank test was used for time-to-event analysis., Results: During the current era (2000 through 2004), D+ /R- (n = 951), D+/- /R+ (n = 2,676), and D- /R- (n = 772) exhibited no differences in survival (p = 0.561), with rates of death per 100 patient-years of 16.6 (95% confidence interval, 14.9 to 18.5), 15.0 (95% confidence interval, 14.0 to 16.0), and 14.7 (95% confidence interval, 13.0 to 16.6), respectively. However, survival was significantly different for groups in the earlier eras of 1990 through 1994 (p < 0.001) and 1995 through 1999 (p < 0.001). During the three periods, survival improved significantly in D+ /R- (p < 0.001) and D+/- /R+ (p < 0.001), but survival in D- /R- (p = 0.351) did not change significantly with time., Conclusions: In the current era, survival after lung transplantation is statistically equivalent regardless of CMV match status. Although in previous eras survival was worse among the D+/- /R+ and D+ /R- groups, in this era of aggressive CMV prophylaxis, CMV mismatch should not be sufficient grounds to decline a lung allograft offer.

Neuronal firing patterns are determined by the cell's intrinsic electrical and morphological properties and are regulated by synaptic interactions. While the properties of cerebellar neurons have generally been studied in much detail, little is known about the unipolar brush cells (UBCs), a type of glutamatergic interneuron that is enriched in the granular layer of the mammalian vestibulocerebellum and participates in the representation of head orientation in space. Here we show that UBCs can be distinguished from adjacent granule cells on the basis of differences in membrane capacitance, input resistance and response to hyperpolarizing current injection. We also show that UBCs are intrinsically firing neurons. Using action potential clamp experiments and whole-cell recordings we demonstrate that two currents contribute to this property: a persistent TTX-sensitive sodium current and a ruthenium red-sensitive, TRP-like cationic current, both of which are active during interspike intervals and have reversal potentials positive to threshold. Interestingly, although UBCs are also endowed with a large I(h) current, this current is not involved in their intrinsic firing, perhaps because it activates at voltages that are more hyperpolarized than those associated with autonomous activity.

Objectives: (1) To examine the interaction of donor age with ischemic time and their effect on survival and (2) to define ranges of ischemic time associated with differences in survival., Methods: The United Network for Organ Sharing provided de-identified patient-level data. The study population included 33,640 recipients undergoing heart transplantation between October 1, 1987, and December 31, 2004. Recipients were divided by donor age into terciles: 0 to 19 years (n = 10,814; 32.1%), 20 to 33 years (11,410, 33.9%), and 34 years or more (11,416, 33.9%). Kaplan-Meier survival functions and Cox regression were used for time-to-event analysis. Receiver operating characteristic curves and stratum-specific likelihood ratios were generated to compare 5-year survival at various thresholds for ischemic time., Results: In univariate Cox proportional hazards regression, the effect of ischemic time on survival varied by donor age tercile: 0 to 19 years (P = .141), 20 to 33 years (P < .001), and 34 years or more (P < .001). These relationships persisted in multivariable regression. Threshold analysis generated a single stratum (0.37-12.00 hours) in the 0- to 19-year-old group with a median survival of 11.4 years. However, in the 20- to 33-year-old-group, 3 strata were generated: 0.00 to 3.49 hours (limited), 3.50 to 6.24 hours (prolonged), and 6.25 hours or more (extended), with median survivals of 10.6, 9.9, and 7.3 years, respectively. Likewise, 3 strata were generated in the group aged 34 years or more: 0.00 to 3.49 (limited), 3.50 to 5.49 (prolonged), and 5.50 or more (extended), with median survivals of 9.1, 8.5, and 6.3 years, respectively., Conclusions: The effect of ischemic time on survival after heart transplantation is dependent on donor age, with greater tolerance for prolonged ischemic times among grafts from younger donors. Both donor age and anticipated ischemic time must be considered when assessing a potential donor.

Background: The incidence of coronary artery bypass graft surgery (CABG) performed in elderly patients has been increasing over recent years. We sought to evaluate clinical outcomes of octogenarians undergoing CABG using an audited state-wide mandatory database., Methods: New York State Department of Health's Cardiac Reporting System was analyzed from 1998 to 2002. In all, 88,154 patients undergoing isolated CABG were identified. Patients were divided into four age groups: less than 50 years (group 1, n = 6,527), 50 to 64 years (group 2, n = 30,088), 65 to 79 years (group 3, n = 43,369), and 80 years and above (group 4, n = 8,170)., Results: Of all patients, 9.3% were octogenarians. In addition to marginally worse coronary artery disease, octogenarians generally manifested a higher incidence of preoperative risk factors such as cerebrovascular disease, peripheral vascular disease, and congestive heart failure compared with younger patients at baseline. Both length of hospital stay and in-hospital mortality rate were significantly higher among octogenarians. The incidence of postoperative complications was higher among octogenarians. Multivariate analysis demonstrated renal failure requiring dialysis (odds ratio [OR] = 4.4), myocardial infarction within 6 hours before surgery (OR = 3.6), chronic obstructive pulmonary disease (OR = 1.7), congestive heart failure at admission (OR = 1.7), emergent operation (OR = 1.6), Canadian Cardiovascular Society functional class IV (OR = 1.5), hypertension (OR = 1.4), and low ejection fraction (OR = 0.98) to be significant independent predictors of in-hospital mortality of octogenarians. Discharge to home rates were significantly lower for octogenarians., Conclusions: Although early outcomes in octogenarians are acceptable, these factors alone are not sufficient to reflect overall success of CABG in these patients, given the strikingly lower discharge to home rates. Attention to full functional recovery in octogenarians is essential.

Surgical atrial fibrillation ablation (SAFA) has not achieved the efficacy of Cox's original maze procedure, although technical improvements continue to be made. It is possible that biologic factors determine SAFA success. Therefore we examined how patient-specific characteristics affected SAFA success in 353 atrial fibrillation (AF) patients who underwent SAFA at a single institution. Among these, 257 (72.8%) had continuous AF and 96 (27.2%) had intermittent AF. For 297 patients (84.1%) postoperative follow-up was > 3 months. We compared SAFA success in patients whose procedure involved only pulmonary vein isolation with those whose procedure involved extensive lesion sets. Multivariate analysis included AF duration, left atrial size, preoperative atrial flutter, concomitant procedures, lesion sets, and energy source. Early SAFA success was classified as freedom from AF between postoperative months 3 and 6, and intermediate success between postoperative months 6 and 12. Receiver-operating characteristic (ROC) curves and stratum-specific likelihood ratios (SSLR) were generated to compare intermediate failure by left atrial size (LAS) thresholds. SAFA was more successful in the intermittent than the continuous AF group (n = 66, 86% vs n = 165, 71%; P = .014). When pulmonary vein isolation was compared only to more extensive lesion sets, there was no difference in success in the intermittent (34, 91% vs 32, 81%; P = .24) or continuous groups (67, 73% vs. 98, 69%; P = .603). Success for intermittent AF patients was not correlated with variables considered; in continuous AF patients, predictors included presence of concomitant mitral valve repair/replacement (P = .075), decreasing LAS (P = .025) and absence of preoperative atrial flutter (P = .001). In the continuous AF group, ROC curves and corresponding areas under the curve (AUC) were 0.60 (0.50-0.71) for failure at 6 months to 1 year. SSLR analysis generated 2 strata for LAS: < 8 cm with SSLR = 0.87 (0.74-1.0) and < or = 8 cm SSLR = 2.98 (1.07-8.3). In patients with intermittent AF, SAFA achieved acceptable results regardless of tested preoperative and intraoperative variables. In continuous AF, patient-specific characteristics affected success more than intraoperative variables. Failure was more than 3-fold greater in continuous AF patients with an LAS < or = 8 cm. In both patient types, more extensive lesion sets were not shown to improve outcomes. Future improvements in SAFA may depend on pharmacologic and/or surgical substrate modification.

Background: Minimally invasive cardiac surgical procedures have become ubiquitous over the past decade. In many cases, these techniques have been associated with decreased morbidity, shorter length of stay, decreased pain, faster recovery, and superior cosmetic results. The purpose of this study was to compare outcomes using a minimally invasive (mini-thoracotomy) versus standard (sternotomy) approach to the surgical resection of atrial masses., Methods: Analysis was based on 34 consecutive patients who underwent atrial mass resection at the New York-Presbyterian Hospital/Columbia Presbyterian Medical Center in New York, NY. The reference (REF) group included 18 patients who underwent excision of an atrial mass via a standard approach (sternotomy). The minimally invasive (MI) group included 16 patients who underwent excision of an atrial mass via a mini-thoracotomy., Results: There were no statistically significant differences between the REF and MI groups based on demographic or preoperative characteristics. Tissue diagnosis of the masses resected included myxoma (n = 24), fibroblastoma (n = 3), B-cell lymphoma (n = 1), and other benign masses (n = 6). Cardiopulmonary bypass (70.5 versus 76.5 minutes; P = .57) and aortic cross-clamp times (32.7 versus 47.3 minutes; P = .14) did not differ significantly between the REF and MI groups, nor did intraoperative transfusion of packed red blood cells (0.35 versus 0.38 units; P = .93). As assessed by intraoperative trans-esophageal echocardiogram, there were no moderate to severe valvular abnormalities observed following chest closure. Intensive care unit length of stay (46.1 versus 26.2 hours; P = .15), overall hospital length of stay (6.39 versus 5.06 days; P= .18), and time to extubation (0.78 versus 0.44 days; P = .44) all trended toward shorter duration in the MI group compared with the REF group-although none of these differences achieved statistical significance. Postoperative transthoracic echocardiograms were obtained in 14 of 34 (41.2%) patients; none revealed any new or significant abnormalities. All patients survived to hospital discharge; one patient in the REF group expired during the follow-up period. Among the 34 patients, 26 patients (76.4%) were at least 2 years postoperative from their resection; 25 of the 26 (96.1%) were alive at 2-year follow-up, and the remaining 8 were alive at 1-year follow-up. All patients were free of recurrence at last follow-up. CONCLUSIONS. Minimally invasive atrial mass excisions can be accomplished reliably without compromising complete tumor resection and without significant increases in operative times or serious adverse events. In addition, measures of recovery time in this study suggest faster recovery among the MI group, which is consistent with the proposed advantages by proponents of minimally invasive surgery.

Purpose: The purpose of this study was to evaluate diffusing tip laser energy in surgical atrial fibrillation ablation using a canine model. This is the first report to describe the pathological and histological findings using a laser energy source., Description: The surgical atrial fibrillation ablation procedure was performed through a left atriotomy; the pulmonary veins were encircled in 16 dogs using a diode laser (980 nm) with a diffusing tip that permits linear ablation perpendicular to the fiber direction. Lesion durations were 45 seconds with a power density of 3.8 or 4.5 W/cm. Six animals were allowed to survive 4 hours after the procedure, with the remainder sacrificed at 1 week (n = 1), 4 weeks (n = 3), and 6 weeks (n = 6). Electrophysiologic effectiveness was judged using unipolar or bipolar pacing from the pulmonary veins after attempting isolation. Hearts were harvested for histologic examination using standard trichrome staining., Evaluation: All animals tolerated the procedure. The animals required an average of 5.6 +/- 0.82 lesions to complete the procedure. All animals had confirmed isolation of the pulmonary veins as judged by unipolar or bipolar pacing, and this isolation persisted in those animals that were allowed to survive. Pathology revealed all lesions to be transmural with an average tissue thickness of 3.62 +/- 1.50 mm (range, 0.95 mm to 7.06 mm)., Conclusions: Diffusing tip laser technology reproducibly makes rapid, transmural, and electrophysiologically effective atrial lesions.

Objectives: A critical shortage of donor organs has caused many centers to use less restrictive donor criteria, including the use of adult-age donors for pediatric recipients. The purpose of this study is (1) to describe the supply of pediatric (0-18 years) heart donors, (2) to explore the relationship between donor age and long-term survival, and (3) to define threshold age ranges associated with decreased long-term survival., Methods: The United Network of Organ Sharing provided deidentified patient-level data. Primary analysis focused on 1887 heart transplant recipients aged 9 to 18 years undergoing transplantation from October 1, 1987, to September 25, 2005. Kaplan-Meier analysis and log-rank tests were used in time-to-event analysis. Receiver operating characteristic curves and stratum-specific likelihood ratios were generated to compare survival at various donor age thresholds., Results: The number of pediatric donors decreased (P < .001) over the study period, particularly from 1993 (n = 640) through 2004 (n = 432). Among recipients aged 9 to 18 years, univariate analysis demonstrated a statistically significant (P < .001) inverse relationship between donor age and survival. Stratum-specific likelihood ratio analysis generated 3 strata for donor age: the low-risk, intermediate-risk, and high-risk groups consisted of donors aged 13 years or younger (n = 611, 32.41%), 14 to 51 years (n = 1258, 66.7%), and 52 years and older (n = 16, 0.85%), respectively. In the low-risk, intermediate-risk, and high-risk groups median survival was 4069 days (11.1 years), 3495 days (9.57 years), and 1197 days (3.28 years), respectively., Conclusions: Although donors aged 13 years or less offer pediatric recipients the best chance for achieving long-term survival, donors aged 14 to 51 years offer good outcomes to pediatric recipients. Consideration should be given to expanded use of well-selected adult-age donors for pediatric recipients.