Allan S. Stewart

Survival After Heart Transplantation Is Not Diminished Among Recipients With Uncomplicated Diabetes Mellitus An Analysis of the United Network of Organ Sharing Database

Background— This study compares posttransplantation outcomes of survival and morbidity among recipients with and without diabetes mellitus (DM). Methods and Results— The United Network of Organ Sharing (UNOS) provided deidentified patient-level data. Primary analysis focused on 20 412 first-time heart transplant recipients aged ≥18 years who underwent transplantation between January 1, 1995, and December 31, 2005. To determine severity of DM, DM recipients were stratified by their aggregate number of diabetes-related complications (DRCs), including pretransplantation history of renal failure (serum creatinine=2.5 mg/dL), peripheral vascular disease, cerebrovascular accident, and severe obesity (body mass index ≥35 kg/m2). Kaplan-Meier analysis was performed to compare time to event. Although posttransplantation survival was significantly better (P<0.001) among patients without DM (median survival 10.1 years) than among those with DM (9.0 years), survival did not differ (P=0.08) between those without DM (10.1 years) and those with uncomplicated DM (0 DRCs; 9.3 years). Among those with DM, survival was worse with each additional DRC: 0 DRC, 9.3 years; 1 DRC, 6.7 years; and ≥2 DRCs, 3.6 years. Although acute rejection and transplant coronary artery disease–free survival did not differ between groups, renal failure and severe infection-free survival were worse in those with DM and were inversely related to the number of DRCs. Conclusions— Posttransplantation survival among patients with uncomplicated DM was not significantly different than that among nondiabetics. However, when stratified by disease severity, recipients with more severe diabetes had significantly worse survival than nondiabetics. Therefore, although DM alone should not be a contraindication to heart transplantation, given the critical shortage of transplantable organs, maximal benefit may be achieved by exploring alternative treatment options in patients with severe DM. These include use of high-risk transplant lists and destination therapy.

Posttransplant survival is not diminished in heart transplant recipients bridged with implantable left ventricular assist devices

BACKGROUNDnThe 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).nnnMETHODSnThe 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.nnnRESULTSnIn 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.nnnCONCLUSIONnThe 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.

Role of the Abiomed BVS 5000 device for short-term support and bridge to transplantation

Over the last 10 years, we have gained experience implanting the Abiomed BVS 5000 (Abiomed, Inc., Danvers, MA) device for short-term mechanical support. We retrospectively reviewed our experience with this device. From April 1993 through January 2003, 71 patients underwent implantation of an Abiomed BVS 5000 device. This included 19 left ventricular assist devices (LVADs), 30 right ventricular assist devices (RVADs), and 22 biventricular assist devices (BIVADs). Demographics of device recipients, conditions for mechanical support, and outcome were evaluated for each device type.Devices were inserted for postcardiotomy cardiogenic shock in 53 (74.6%) patients and precardiotomy cardiogenic shock in 18 (25.4%) patients. Mean duration of support was 4.9 ± 4.1 days, with 64 (90.1%) patients supported for fewer than 10 days. Twenty-nine (40.8%) patients were successfully weaned from support after myocardial recovery: 7 (36.8%) LVADs, 13 (43.3%) RVADs, and 9 (40.9%) BIVADs. Eight (11.3%) patients received devices as a “bridge to bridge,” undergoing implantation of a long-term HeartMate LVAD (Thoratec, Pleasanton, CA): six (31.6%) LVADs and two (9.1%) BIVADs. Seven (9.9%) Abiomed patients were successfully bridged to transplantation: two (10.5%) LVADs, two (6.7%) RVADs, and three (13.6%) BIVADs. Overall, 44 (62.0%) patients survived support: weaned, “bridged to bridge,” or transplanted.The Abiomed BVS 5000 can be used effectively for short-term stabilization and for bridging to transplant in select patients.

Matching high-risk recipients with marginal donor hearts is a clinically effective strategy.

BACKGROUNDnThe 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.nnnMETHODSnThe 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.nnnRESULTSnSurvival 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).nnnCONCLUSIONSnAlternate 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.

The lymphocytic infiltration in calcific aortic stenosis predominantly consists of clonally expanded T cells.

Valve lesions in degenerative calcific aortic stenosis (CAS), a disorder affecting 3% of those older than 75 years, are infiltrated by T lymphocytes. We sought to determine whether the αβ TCR repertoire of these valve-infiltrating lymphocytes exhibited features either of a polyclonal nonselective response to inflammation or contained expanded clones suggesting a more specific immune process. TCR β-chain CDR3-length distribution analysis using PCR primers specific for 23 Vβ families performed in eight individuals with CAS affecting tri- or bileaflet aortic valves revealed considerable oligoclonal T cell expansion. In five cases, β-chain nucleotide sequencing in five selected Vβ families showed that an average of 92% of the valve-infiltrating T cell repertoire consisted of expanded T cell clones, differing markedly in composition from the relatively more polyclonal peripheral CD8 or CD4 T cell subsets found even in this elderly population. Twenty-four of the valve-infiltrating T cell clones also had the same clone identified in blood, some of which were highly expanded. Interestingly, 22 of these 24 shared clones were CD8 in lineage (p = 1.5 × 10−12), suggesting a possible relationship to the expanded CD8+CD28− T cell clones frequently present in the elderly. Additionally, the sequences of several TCR β-chain CDR3 regions were homologous to TCR β-chains identified previously in allograft arteriosclerosis. We infer that these findings are inconsistent with a nonselective secondary response of T cells to inflammation and instead suggest that clonally expanded αβ T cells are implicated in mediating a component of the valvular injury responsible for CAS.

Circulating Activated and Effector Memory T Cells Are Associated with Calcification and Clonal Expansions in Bicuspid and Tricuspid Valves of Calcific Aortic Stenosis

We sought to delineate further the immunological significance of T lymphocytes infiltrating the valve leaflets in calcific aortic stenosis (CAS) and determine whether there were associated alterations in circulating T cells. Using clonotypic TCR β-chain length and sequence analysis we confirmed that the repertoire of tricuspid CAS valves contains numerous expanded T cell clones with varying degrees of additional polyclonality, which was greatest in cases with severe calcification. We now report a similar proportion of clonal expansions in the much younger bicuspid valve CAS cases. Peripheral blood flow cytometry revealed elevations in HLA-DR+ activated CD8 cells and in the CD8+CD28nullCD57+ memory-effector subset that were significantly greater in both bicuspid and tricuspid CAS cases with more severe valve calcification. Lesser increases of CD4+CD28null T cells were identified, principally in cases with concurrent atherosclerotic disease. Upon immunostaining the CD8 T cells in all valves were mainly CD28null, and CD8 T cell percentages were greatest in valves with oligoclonal repertoires. T cell clones identified by their clonotypic sequence as expanded in the valve were also found expanded in the circulating blood CD28nullCD8+ T cells and to a lesser degree in the CD8+CD28+ subset, directly supporting the relationship between immunologic events in the blood and the valve. The results suggest that an ongoing systemic adaptive immune response is occurring in cases with bicuspid and tricuspid CAS, involving circulating CD8 T cell activation, clonal expansion, and differentiation to a memory-effector phenotype, with trafficking of T cells in expanded clones between blood and the valve.

Quality, not volume, determines outcome of coronary artery bypass surgery in a university-based community hospital network

OBJECTIVESnThe present study examined the relationship between hospital and surgeon coronary artery bypass grafting procedural volume, mortality, morbidity, and National Quality Forum care processes in a university-based community hospital quality improvement program.nnnMETHODSnThe study population consisted of 2218 consecutive patients undergoing isolated coronary artery bypass grafting from 2007 to 2009 in a university-based quality improvement program that emphasizes involvement of all surgeons in the academic quality endeavor. The endpoints included operative mortality, major morbidity, and National Quality Forum-endorsed process measures as defined by the Society of Thoracic Surgeons. The procedural volume was analyzed as a categorical and continuous variable using general estimating equations, which accounted for clustering effects and which were adjusted for Society of Thoracic Surgeons risk scores and the propensity for operation in a low- versus high-volume program.nnnRESULTSnThe annual program volume ranged from 67 to 292 (median, 136; interquartile range, 88-224) and surgeon volume from 1 to 124 (median, 58; interquartile range, 30-89). The mortality rate among the hospitals was 0.47% to 2.23% (0.8% overall), and the observed/expected mortality ranged from 0 to 1.20 (0.41 overall). When comparing low-volume (<200 cases/year) and high-volume centers, no difference was found in the mortality (odds ratio [OR], 1.08; 95% confidence interval [CI], 0.46-2.54, P = .85), morbidity (OR, 1.34; 95% CI, 0.73-2.43), or any of the medication process measures. No difference was found in mortality (OR, 1.59; 95% CI, 0.81-3.13; P = .18), morbidity (OR, 1.20; 95% CI, 0.86-1.66; P = .28), or medication failure (OR, 0.57, 95% CI, 0.3-1.10; P = .10) between the high- and low-volume surgeons (<87). After adjustment for both the Society of Thoracic Surgeons risk score and the propensity score, no association was found for either hospital or surgeon volume with mortality or morbidity. However, a lack of compliance with National Quality Forum measures was highly predictive of morbidity (OR, 1.51; 95% CI, 1.18-1.93; P = .001), regardless of volume, even after adjustment for predicted risk.nnnCONCLUSIONSnIn the setting of a university-based community hospital quality improvement program, excellent surgical results can consistently be obtained even in relatively low-volume programs. The surgical outcomes were not associated with program or surgeon volume, but were directly correlated with the focus on quality as manifested by compliance with evidence-based quality standards. Meaningful university affiliation might represent a new quality paradigm for cardiac surgery in the community hospital setting.

Modified Bentall operation with bioprosthetic valved conduit: Columbia University experience.

A conduit was made by sewing a bovine pericardial valve into a graft conduit with the pseudo-sinuses of Valsalva. The graft collar below the valve cuff ring was sewn to the aortic annulus with interrupted pledgeted sutures. From August 2005 to February 2008, 68 patients underwent aortic root replacements with this technique. Operative mortality was 2.9% (2 acute aortic dissection patients died). During median follow-up of 11 months, 1 patient had reoperation for conduit failure due to infectious endocarditis. This technique is safe and feasible with favorable early outcomes. Because the valve is sewn above the outflow tract, superior hemodynamics are achieved. Reoperation may be accomplished by removal of the valve rather than full root re-replacement.

Simplified placement of multiple artificial mitral valve chords.

BACKGROUNDnThe use of artificial chords for the replacement of diseased mitral valve chordae and the correction of anterior and posterior leaflet prolapse is well described, although it is infrequently applied because of technical challenges.nnnMETHODSnA simplified approach to attaching the new chords to a single papillary muscle base within the left ventricle has been reported, and we present a series of 13 patients with moderate-severe mitral regurgitation (MR) who underwent chordal replacement using this improved technique.nnnRESULTSnThe MR grade by echocardiogram improved from 3.7 +/- 0.4 preoperatively to 1.0 +/- 0.8 postoperatively. All patients were doing well at a mean follow-up interval of 285 +/- 62 days.nnnCONCLUSIONnChordal replacement for both anterior and posterior leaflet prolapse is an effective treatment for MR when combined with standard mitral valve repair techniques. The authors technique of determining proper chordal height and placing multiple chordae is also discussed.

Short-term outcomes in adult cardiac surgery in the use of del Nido cardioplegia solution.

Objectives: Del Nido cardioplegia in adult cardiac surgery has not been studied although it has been in common use as a “single” dose cardioplegia in pediatric heart surgery. We retrospectively assessed the short-term (in-hospital) clinical outcomes of patients undergoing aortic valve replacement (AVR) using del Nido cardioplegia solution, comparing it to conventional multi-dose whole blood cardioplegia. Methods: We switched our cardioplegia protocol from conventional whole blood cardioplegia exclusively to del Nido solution in May 2011. In 2011, 240 consecutive patients underwent isolated AVR. One hundred and seventy-eight of them were operated on with the use of del Nido cardioplegia (del Nido group) and whole blood cardioplegia (conventional group) was used in the other 62 patients. Isolated AVR was chosen as a cohort because of its relative simplicity and the similarity of surgical techniques among surgeons. Propensity-score matching identified 54 matched pairs for analysis. Results: The retrograde cardioplegia technique was used in 19 cases (35.2%) in the del Nido group and 52 cases (96.3%) in the conventional group (p<0.001). Mean cardiopulmonary bypass time and mean aortic cross-clamp time were significantly shorter in the del Nido group compared to the conventional group: 71 ± 16 min vs. 84 ± 28 min (p<0.01), 52 ± 14 min vs. 60 ± 16 min (p<0.01), respectively. Postoperative inotropic support was required in 11 patients (20.4 %) in the del Nido group and 13 patients (24.1 %) in the conventional group (p=0.82) with no statistical difference. No patient required a postoperative intra-aortic balloon pump and in-hospital mortality was 0% in both groups. There was no significant difference in postoperative complications between the two groups. Conclusions: Short-term outcomes in adult cardiac surgery using del Nido solution were acceptable and comparable to conventional multi-dose whole blood cardioplegia. The del Nido cardioplegia technique was associated with shortened cross-clamp times and less frequent utilization of the retrograde cardioplegia delivery technique.