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Background: As left ventricular assist device (LVAD) survival rates continue to improve, evaluating site-specific variability in outcomes can facilitate identifying targets for quality-improvement initiative opportunities in the field.Methods: Deidentified center-specific outcomes were analyzed for HeartMate 3 (HM3) patients enrolled in the MOMENTUM 3 pivotal and continued access protocol trials. Centers < 25th percentile for HM3 volumes were excluded. Variability in risk-adjusted center mortality was assessed at 90 days and 2 years (conditional upon 90-day survival). Adverse event (AE) rates were compared across centers.Results: In the 48 included centers (1958 patients), study-implant volumes ranged between 17 and 106 HM3s. Despite similar trial-inclusion criteria, patient demographics varied across sites, including age quartile ((Q)1-Q3:57-62 years), sex (73%-85% male), destination therapy intent (60%-84%), and INTERMACS profile 1-2 (16%-48%). Center mortality was highly variable, nadiring at ≤ 3.6% (≤ 25th percentile) and peaking at ≥ 10.4% (≥ 75th percentile) at 90 days and ≤ 10.2% and ≥ 18.7%, respectively, at 2 years. Centers with low mortality rates tended to have lower 2-year AE rates, but no center was a top performer for all AEs studied.Conclusions: Mortality and AEs were highly variable across MOMENTUM 3 centers. Studies are needed to improve our understanding of the drivers of outcome variability and to ascertain best practices associated with high-performing centers across the continuum of intraoperative to chronic stages of LVAD support. [ABSTRACT FROM AUTHOR]

The mitochondrial adenosine triphosphate–sensitive potassium channel is central to pharmacologically induced tolerance to spinal cord injury. We hypothesized that both direct and nitric oxide–dependent indirect activation of the adenosine triphosphate–sensitive potassium channel contribute to the induction of ischemic metabolic tolerance. Spinal cord injury was induced in adult male C57BL/6 mice through 7 minutes of thoracic aortic crossclamping. Pretreatment consisted of intraperitoneal injection 3 consecutive days before injury. Experimental groups were sham (no pretreatment or ischemia, n = 10), spinal cord injury control (pretreatment with normal saline, n = 27), Nicorandil 1.0 mg/kg (direct and indirect adenosine triphosphate–sensitive potassium channel opener, n = 20), Nicorandil 1 mg/kg + carboxy-PTIO 1 mg/kg (nitric oxide scavenger, n = 21), carboxy-PTIO (n = 12), diazoxide 5 mg/kg (selective direct adenosine triphosphate–sensitive potassium channel opener, n = 25), and DZ 5 mg/kg+ carboxy-PTIO 1 mg/kg, carboxy-PTIO (n = 23). Limb motor function was assessed using the Basso Mouse Score (0-9) at 12-hour intervals for 48 hours after ischemia. Motor function was significantly preserved at all time points after ischemia in the Nicorandil pretreatment group compared with ischemic control. The addition of carboxy-PTIO partially attenuated Nicorandil's motor-preserving effect. Motor function in the Nicorandil + carboxy-PTIO group was significantly preserved compared with the spinal cord injury control group (P <.001), but worse than in the Nicorandil group (P =.078). Motor preservation in the diazoxide group was similar to the Nicorandil + carboxy-PTIO group. There was no significant difference between the diazoxide and diazoxide + carboxy-PTIO groups. Both direct and nitric oxide–dependent indirect activation of the mitochondrial adenosine triphosphate–sensitive potassium channel play an important role in pharmacologically induced motor function preservation. [Display omitted] [ABSTRACT FROM AUTHOR]

There are currently no clinically utilized pharmacological agents for the induction of metabolic tolerance to spinal cord ischemia-reperfusion injury in the setting of complex aortic intervention. Nicorandil, a nitric oxide donor and ATP-sensitive potassium (KATP) channel opener, has shown promise in neuroprotection. However, the optimized clinical application of the drug and its mechanism of neuroprotection remains unclear. We hypothesized that 3-days pretreatment would confer the most effective neuroprotection, mediated by mitochondrial KATP channel activation. Spinal cord injury was induced by 7 minutes of thoracic aortic cross-clamping in adult male C57BL/6 mice. Time course: mice received 0.1 mg/kg nicorandil for 10 min, 4 hours, and 3 consecutive days prior to ischemia compared with control. Dose challenge: mice received 3-days nicorandil pretreatment comparing 0.1 mg/kg, 1.0 mg/kg, 5.0 mg/kg, and saline administration. Mitochondrial KATP channel blocker 5-hydroxy-decanoate (5HD) was co-administered to elucidate mechanism. Limb motor function was evaluated, and viable anterior horn neurons quantified. Nicorandil pretreatment at 4 hours and 3 days before ischemia demonstrated significant motor function preservation; administration 10 minutes before ischemia showed no neuroprotection. All nicorandil doses showed significant motor function preservation. Three days administration of Nicorandil 1.0 mg/kg was most potent. Neuroprotection was completely abolished by 5HD co-administration. Histological analysis showed significant neuron preservation with nicorandil pretreatment, which was attenuated by 5HD co-administration. Three days administration of Nicorandil 1.0 mg/kg showed near-total motor function preservation in a murine spinal cord ischemia-reperfusion model, mediated by the mitochondrial KATP channel. [ABSTRACT FROM AUTHOR]

Outcomes in patients with smaller body size after HeartMate 3 left ventricular assist device (HM3) implantation are not well characterized. We sought to evaluate outcomes in smaller vs larger body surface area (BSA) patients in the MOMENTUM 3 pivotal trial and its Continued Access Protocol cohort. The analysis cohort included 1015 HM3 patients divided into 2 groups: BSA ≤1.70 m2 (small patients, n = 82) and BSA >1.70 m2 (large patients, n = 933). The composite primary end point was survival at 2 years free of disabling stroke or reoperation to replace or to remove a malfunctioning device. Adverse events were compared between groups. Smaller patients were more frequently women (56.1% vs 17.7%; P <.001) and had lower prevalence of diabetes (28.1% vs 43.9%; P =.005) and hypertension (51.2% vs 71.9%; P <.001), larger median indexed LVEDD (normalized by BSA, 40 vs 33 mm/m2; P <.001), and lower median serum creatinine concentration (1.1 vs 1.3 mg/dL; P <.001). The proportion of patients achieving the composite end point at 2 years was 77% in both groups (adjusted hazard ratio, 1.14; 95% CI, 0.68-1.91; P =.62). Two-year adverse event rates were also similar between groups except for sepsis (6.1% vs 14.9%; P =.029) and cardiac arrhythmias (24.4% vs 35.3%; P =.005), which were higher in the larger patients. Outcomes after HM3 implantation were comparable between small and large patients. Smaller body size should not be used to deny HM3 implantation in patients who are otherwise suitable candidates for durable mechanical circulatory support. [Display omitted] [ABSTRACT FROM AUTHOR]

The treatment of left main (LM) coronary artery disease (CAD) requires complex decision-making. Recent clinical practice guidelines provide clinicians with guidance; however, decisions regarding treatment for individual patients can still be difficult. The American College of Cardiology's Cardiac Surgery Team and Interventional Council joined together to develop a practical approach to the treatment of LM CAD, taking into account randomized clinical trial, meta-analyses, and clinical practice guidelines. The various presentations of LM CAD based on anatomy and physiology are presented. Recognizing the complexity of LM CAD, which rarely presents isolated and is often in combination with multivessel disease, a treatment algorithm with medical therapy alone or in conjunction with percutaneous coronary intervention or coronary artery bypass grafting is proposed. A heart team approach is recommended that accounts for clinical, procedural, operator, and institutional factors, and features shared decision-making that meets the needs and preferences of each patient and their specific clinical situation. [ABSTRACT FROM AUTHOR]

Reimbursement for cardiothoracic surgery continues to be threatened with enormous financial cuts ranging from 5% to 10% in recent years. In this policy perspective, we describe the history of reimbursement for cardiothoracic surgery, highlight areas in need of urgent reform, propose possible solutions that Congress and the Executive Branch may enact, and call cardiothoracic surgeons to action on this critical issue. Meaningful engagement of members of The Society of Thoracic Surgeons with their elected representatives is the only way to prevent these cuts. [Display omitted] [ABSTRACT FROM AUTHOR]

The Society of Thoracic Surgeons (STS) original coronary artery bypass graft surgery (CABG) composite measure uses a 1-year analytic cohort and 98% credible intervals (CrI) to classify better than expected (3-star) performance or worse than expected (1-star) performance. As CABG volumes per STS participant (eg, hospital or practice group) have decreased, it has become more challenging to classify performance categories using this approach, especially for lower volume programs, and alternative approaches have been explored. Among 990 STS Adult Cardiac Surgery Database participants, performance classifications for the CABG composite were studied using various analytic cohorts: 1 year (current approach, 2017); 3 years (2015 to 2017); last 450 cases within 3 years; and most recent year (2017) plus additional cases to 450 total. We also compared 98% CrI with 95% CrI (used in other STS composite measures). Using 3 years of data and 95% CrIs, 113 of 990 participants (11.4%) were classified 1-star and 198 (20%) 3-star. Compared with 1-year analytic cohorts and 98% CrI, the absolute and relative increases in the proportion of 3-star participants were 14 percentage points and 233% (n = 198 [20%] vs n = 59 [6%]). Corresponding changes for 1-star participants were 6.5 percentage points and 133% (n = 113 [11.4%] vs n = 48 [4.9%]). These changes were particularly notable among lower volume (fewer than 199 CABG per year) participants. Measure reliability with the 3-year, 95% CrI modification is 0.78. Compared with current STS CABG composite methodology, a 3-year analytic cohort and 95% CrI increases the number and proportion of better or worse than expected outliers, especially among lower-volume Adult Cardiac Surgery Database participants. This revised methodology is also now consistent with other STS procedure composites. [ABSTRACT FROM AUTHOR]

Failure to rescue (FTR) focuses on the ability to prevent death among patients who have postoperative complications. The Society of Thoracic Surgeons (STS) Quality Measurement Task Force has developed a new, risk-adjusted FTR quality metric for adult cardiac surgery. The study population was taken from 1118 STS Adult Cardiac Surgery Database participants including patients who underwent isolated CABG, aortic valve replacement with or without CABG, or mitral valve repair or replacement with or without CABG between January 2015 and June 2019. The FTR analysis was derived from patients who had one or more of the following complications: prolonged ventilation, stroke, reoperation, and renal failure. Data were randomly split into 70% training samples (n = 89,059) and 30% validation samples (n = 38,242). Risk variables included STS predicted risk of mortality, operative procedures, and intraoperative variables (cardiopulmonary bypass and cross-clamp times, unplanned procedures, need for circulatory support, and massive transfusion). Overall mortality for patients undergoing any of the index operations during the study period was 2.6% (27,045 of 1,058,138), with mortality of 0.9% (8316 of 930,837), 8% (7618 of 94,918), 30.6% (8247 of 26,934), 51.9% (2661 of 5123), and 62.3% (203 of 326), respectively, among patients having none, one, two, three, or four complications. The FTR risk model calibration was excellent, as were model discrimination (c-statistic 0.806) and the Brier score (0.102). Using 95% Bayesian credible intervals, 62 participants (5.6%) performed worse and 53 (4.7%) performed better than expected. A new risk-adjusted FTR metric has been developed that complements existing STS performance measures. The metric specifically assesses institutional effectiveness of postoperative care, allowing hospitals to target quality improvement efforts. [ABSTRACT FROM AUTHOR]

The Society of Thoracic Surgeons (STS) Adult Cardiac Surgery Database (ACSD) is the largest cardiac surgical database in the world. Linked data from STS ACSD and the Centers for Medicare and Medicaid Services (CMS) database were used to determine contemporary completeness, penetration, and representativeness of STS ACSD. Variables common to both STS and CMS databases were used to link STS procedures to CMS data for all CMS coronary artery bypass grafting surgery (CABG) discharges between 2000 and 2018, inclusive. For each CMS CABG hospitalization, it was determined whether a matching STS record existed. Center-level penetration (number of CMS sites with at least 1 matched STS participant divided by total number of CMS CABG sites) increased from 45% in 2000 to 95% in 2018. In 2018, 949 of 1004 CMS CABG sites (95%) were linked to an STS site. Patient-level penetration (number of CMS CABG hospitalizations at STS sites divided by total number of CMS CABG hospitalizations) increased from 51% in 2000 to 97% in 2018. In 2018, 68,584 of 70,818 CMS CABG hospitalizations (97%) occurred at an STS site. Completeness of case inclusion at STS sites (number of CMS CABG cases at STS sites linked to STS records divided by total number of CMS CABG cases at STS sites) increased from 88% in 2000 to 98% in 2018. In 2018, 66,673 of 68,108 CMS CABG hospitalizations at STS sites (98%) were linked to an STS record. Linkage of the STS and CMS databases demonstrates high and increasing penetration and completeness of STS ACSD. STS ACSD now includes 97% of CABG in the United States. [Display omitted] [ABSTRACT FROM AUTHOR]

Baseline kidney function is a key predictor of postoperative morbidity and mortality. Whether an increased creatinine at the time of surgery, compared with the lowest creatinine in the 3 months before surgery, is associated with poor outcomes has not been evaluated. We examined whether creatinine elevations from "baseline" were associated with adverse postoperative outcomes. A total of 1486 patients who underwent cardiac surgery at the University of Colorado Hospital between January 2011 and May 2016 met inclusion criteria. "Change in creatinine from baseline" was defined as the difference between the immediate presurgical creatinine value and the lowest creatinine value within 3 months preceding surgery. Outcomes evaluated were in-hospital mortality, postoperative infection, postoperative stroke, development of stage 3 acute kidney injury, intensive care unit length of stay, and hospital length of stay. Outcomes were adjusted using a balancing score to account for differences in patient characteristics. There were significant increases in the odds of postoperative infection (odds ratio, 1.17; confidence interval, 1.02-1.34; per 0.1 mg/dL increase in creatinine), stage 3 acute kidney injury (odds ratio, 1.44; confidence interval; 1.18-1.75), intensive care unit length of stay (odds ratio, 1.13; confidence interval, 1.01-1.26), and hospital length of stay (odds ratio, 1.09; confidence interval, 1.05-1.13). There was a significant increase in mortality in the unadjusted analysis, although not after adjustment using a balancing score. There was no association with postoperative stroke. Elevations in creatinine at the time of surgery above the "baseline" level are associated with increased postoperative morbidity. Baseline creatinine should be established before surgery, and small changes in creatinine should trigger heightened vigilance in the postoperative period. [Display omitted] [ABSTRACT FROM AUTHOR]

The Society of Thoracic Surgeons (STS) Quality Measurement Task Force has developed risk models and composite performance measures for isolated coronary artery bypass grafting (CABG), isolated aortic valve replacement (AVR), isolated mitral valve replacement or repair (MVRR), AVR+CABG, and MVRR+CABG. To further enhance its portfolio of risk-adjusted performance metrics, STS has developed new risk models for multiple valve operations ± CABG procedures. Using July 2011 to June 2019 STS Adult Cardiac Surgery Database data, risk models for AVR+MVRR (n = 31,968) and AVR+MVRR+CABG (n = 12,650) were developed with the following endpoints: Operative Mortality, major morbidity (any 1 or more of the following: cardiac reoperation, deep sternal wound infection/mediastinitis, stroke, prolonged ventilation, and renal failure), and combined mortality and/or major morbidity. Data were divided into development (July 2011 to June 2017; n = 35,109) and validation (July 2017 to June 2019; n = 9509) samples. Predictors were selected by assessing model performance and clinical face validity of full and progressively more parsimonious models. Performance of the resulting models was evaluated by assessing discrimination and calibration. C-statistics for the overall population of multiple valve ± CABG procedures were 0.7086, 0.6734, and 0.6840 for mortality, morbidity, and combined mortality and/or morbidity in the development sample, and 0.6953, 0.6561, and 0.6634 for the same outcomes, respectively, in the validation sample. New STS Adult Cardiac Surgery Database risk models have been developed for multiple valve ± CABG operations, and these models will be used in subsequent STS performance metrics. [ABSTRACT FROM AUTHOR]

Mechanical complications after transcatheter aortic valve replacement are fortunately rare with the current generation of devices. Unfortunately, life-threatening complications will occur and it is the responsibility of operators to be familiar with strategies to prevent and manage these challenging scenarios. Because these cases will not occur often, it is important for us to highlight and talk about those that do occur, to learn best practices in how to manage and prevent them going forward. We can learn much from each other's good crash landings. [ABSTRACT FROM AUTHOR]

Spinal cord injury remains a devastating complication of thoracoabdominal aortic surgery. We previously demonstrated that pretreatment with nicorandil preserved motor function in a murine spinal cord injury model through mitochondrial adenosine triphosphate-sensitive potassium channel activation. We hypothesized that the neuroprotective effect of nicorandil is mediated by downstream generation of reactive oxygen species. Spinal cord injury was induced by 7 minutes of thoracic aortic cross-clamping in adult male C57BL/6 mice. Five groups were evaluated: ischemic control (n = 19); nicorandil 1.0 mg/kg (n = 17); nicorandil 1.0 mg/kg plus N acetyl L-cysteine (NAC [reactive oxygen species scavenger, n = 18)]) 150 mg/kg; NAC 150 mg/kg (n = 13); and sham (n = 10). Limb motor function and the number of viable neurons within the anterior horn of the spinal cord were evaluated. Mice in the sham group showed no functional deficits after surgery. Compared with ischemic control, motor function was significantly preserved in the nicorandil pretreatment group at every timepoint after ischemia. In the nicorandil plus NAC group, the motor-preserving effect of nicorandil was completely abolished (P <.001). Viable neuron quantification showed significant neuron preservation in the nicorandil group (29.± 2.6) compared with the ischemic control group (18.5 ± 2.1, P =.024) and nicorandil plus NAC group (14 ± 8.3, P =.001); no significant difference was observed between the ischemic control group and nicorandil plus NAC group (P = 0.768). Reactive oxygen species generation plays a key role in the nicorandil-induced metabolic tolerance to spinal cord injury. Manipulation of mitochondrial adenosine triphosphate-sensitive potassium channels may lead to improvement in preventing spinal cord injury after thoracoabdominal aortic interventions. [ABSTRACT FROM AUTHOR]

Utilization of multiple arterial grafting (MAG) in the United States is less than 10%. Trainee experience with MAG has not previously been examined. A total of 497 thoracic surgery residents in accredited training programs in March 2019 and 115 who completed residency in 2018 were electronically surveyed regarding their experience with MAG using a radial artery (RA) graft or bilateral internal mammary artery (BIMA) grafts with a skeletonized mammary (SM). Eighty-four (14%) trainees responded: 54% had completed 2+ years of training and 87% declared their focus as cardiac, undecided, or both cardiac and thoracic (CUB). Of all 84 respondents, 76% (n = 64 of 84) had no experience with RA harvest. A total of 35% (n = 29 of 84) had no experience with SM harvest. The majority, 68% (n = 57 of 84), used BIMA grafting in 0% to 5% of cases. A total of 61% (n = 51 of 84) used RA conduit in 0% to 5% of cases. Among trainees with 2+ years of experience, 56% (n = 25 of 45) had performed more than 6 SM takedowns, 18% (n = 8 of 45) had no experience. In trainees with 2+ years, 20% (n = 9 of 45) performed more than 5 RA harvests, while 80% (n = 36 of 45) had no experience. Examining integrated 6-year residents with greater than 3 years of experience, only 33% (n = 5 of 15) performed more than 5% RA grafting. A total of 90% of CUB trainees wanted to perform MAG in practice and 75% felt prepared to do so. Despite substantial variation in MAG training, respondents expressed an overwhelming interest in performing MAG. These data and the reality of MAG utilization in the United States indicate that a more rigorous, standardized approach to MAG training may be required. [Display omitted] [ABSTRACT FROM AUTHOR]

Thrombocytopenia is a risk factor for morbidity and mortality in critically ill patients, and is common after cardiopulmonary bypass (CPB). In this study, we evaluate whether thrombocytopenia after CPB is an independent risk factor for postoperative morbidity and mortality. We retrospectively evaluated 1364 patients requiring CPB at the University of Colorado Hospital between January 2011 and May 2016. Platelet nadir, absolute change in platelets, and percent change in platelets were modeled as continuous variables. Patients with postoperative thrombocytopenia (defined a nadir <75 × 103/μL within 72 hours) were also compared with patients without thrombocytopenia in a propensity-matched model. The primary outcome was in-hospital mortality, and secondary outcomes included postoperative infection, postoperative acute kidney injury (AKI), postoperative stroke, and prolonged intensive care unit (ICU) and hospital lengths of stay (LOS). Postoperative thrombocytopenia occurred in 356 (26.0%) patients. In multivariable analysis, platelet nadir was significantly inversely associated with mortality (odds ratio [OR], 0.955; 95% confidence interval [CI], 0.934-0.975; P <.001), postoperative infection (OR, 0.992; 95% CI, 0.986-0.999; P =.03), AKI (all stage) (OR, 0.993; 95% CI, 0.988-0.998; P =.01), AKI (stage 3) (OR, 0.966; 95% CI, 0.951-0.982; P <.001), postoperative stroke (OR, 0.974; 95% CI, 0.956-0.992; P =.006), prolonged ICU stay (OR, 0.986; 95% CI, 0.981-0.991; P <.001), and hospital LOS (OR, 0.998; 95% CI, 0.997-0.999; P =.001). Percent change in platelets from baseline was also significantly associated with all primary and secondary outcomes. Postoperative thrombocytopenia is independently associated with postoperative mortality, AKI, infection, stroke, and prolonged ICU and hospital LOS. Serial platelet monitoring may help identify patients at higher risk of postoperative complications. Further studies investigating strategies to reduce postoperative thrombocytopenia, including reducing CPB time, are needed. [ABSTRACT FROM AUTHOR]

The frozen elephant trunk technique facilitates repair of aortic arch and proximal descending aortic pathologic processes. Commercially available hybrid grafts may simplify this approach by allowing for a single suture line, potentially streamlining the distal anastomosis and improving operative times. However, these devices are currently not readily available in United States. We developed a surgical technique, the Buffalo Trunk, to simplify the frozen elephant trunk procedure that obviates the need for a hybrid graft and decreases operating times. Our technique uses a soft-branched graft along with a stent graft to create a distal anastomosis that incorporates the aorta, stent graft, and soft graft in a zone 2 arch reconstruction. Patient characteristics, operative times, and perioperative outcomes were analyzed. A total of 37 patients underwent the Buffalo Trunk procedure compared with 29 patients who underwent the traditional frozen elephant trunk. Bypass and circulatory arrest times were 34 and 18 minutes shorter, respectively, in the Buffalo Trunk group. Total blood transfusions were lower in the Buffalo Trunk group. The stroke rate was 5% and 30-day mortality occurred in 2 patients. No difference was noted in end-organ dysfunction, morbidity, and mortality between the two techniques. The benefits of a hybrid approach to the frozen elephant trunk can be attained without the complex industry-available technology as presented by our technique, the Buffalo Trunk. Evolution of this approach has facilitated shorter circulatory arrest time and subsequently overall decreased operative times without compromising outcomes. [ABSTRACT FROM AUTHOR]

Our objective was to evaluate the association of bridge to transplant (BTT) extracorporeal membrane oxygenation (ECMO) on survival after lung transplantation (LTx) and determine the degree to which transplant center volume affects this relationship. Using the United Network for Organ Sharing database, we performed a retrospective cohort study evaluating the survival of patients undergoing LTx between 2005 and 2017. On the basis of previous literature, LTx centers were classified into 3 groups using their average annual LTx volume over the preceding 5 years: less than 25, 25 to 49, and more than 50. Survival of BTT ECMO and non-ECMO patients was analyzed using a log-rank test. Propensity scores for BTT ECMO were calculated, and a weighted proportional hazards model was used to compare BTT ECMO and non-ECMO patients by center volume. There were 20,976 patients who met inclusion criteria, with 611 (2.9%) undergoing BTT ECMO. Overall, BTT ECMO was associated with increased posttransplantation hazard of mortality (hazard ratio, 1.37; 95% confidence interval, 1.14 to 1.64). Kaplan-Meier plots by center volume suggest that BTT ECMO–associated mortality may be mitigated at high-volume LTx centers. In the propensity score–weighted proportional hazards model, we determined that when centers perform more than 35 LTxs per year, the increased hazard of BTT ECMO on mortality is no longer observed. BTT ECMO can be performed as a bridge to LTx without significantly increasing patient mortality in high-volume centers. Patients undergoing BTT ECMO at LTx centers that perform more than 35 LTxs annually have equivalent mortality to those who do not require ECMO before transplantation. [ABSTRACT FROM AUTHOR]

Background Delayed paraplegia remains a feared complication of thoracoabdominal aortic intervention. Pharmacologic preconditioning with diazoxide (DZ), an adenosine 5′-triphosphate–sensitive potassium channel opener, results in neuroprotection against ischemic insult. However, the effects of DZ in spinal cord ischemia-reperfusion injury have not been fully elucidated. We hypothesized that DZ attenuates spinal cord ischemia-reperfusion injury through the signaling transducer and activator of transcription (STAT) 3 pathway. Methods Adult male C57/BL6 mice received DZ (20 mg/kg) by oral gavage. Spinal cords were harvested at 0, 12, 24, 36, 48, and 60 hours after administration of DZ. The expression of phosphorylated STAT3 was assessed by Western blot analysis. Five groups were studied: DZ (DZ pretreatment, n = 8), ischemic control (phosphate-buffered saline pretreatment, n = 11), DZ + STAT3 inhibitor LY5 (DZ pretreatment + LY5, n = 8), LY5 (phosphate-buffered saline pretreatment + LY5, n = 8), and sham (without cross-clamping, n = 5). Spinal cord ischemia was induced by 4 minutes of thoracic aortic cross-clamp. Functional scoring (Basso Mouse Score) was done at 12-hour intervals until 48 hours, and spinal cords were harvested for the evaluation of B-cell lymphoma 2 expression and histologic changes. Results The expression of phosphorylated STAT3 was significantly upregulated 36 hours after the administration of DZ. The motor function in the DZ group was significantly preserved compared with all other groups. The expression of B-cell lymphoma 2 in the DZ group was significantly higher than in the ischemic control, DZ + LY5, and LY5 groups 48 hours after reperfusion. Conclusions DZ preserves motor function in spinal cord ischemia-reperfusion injury by the STAT3 pathway. DZ may be beneficial clinically for use in spinal protection in aortic intervention. [ABSTRACT FROM AUTHOR]

Correction of valvular disease is often undertaken during left ventricular assist device (LVAD) implantation with uncertain benefit. We analyzed clinical outcomes with HeartMate 3 (HM3; Abbott) LVAD implantation in those with various concurrent valve procedures (HM3+VP) with those with an isolated LVAD implant (HM3 alone). The study included 2200 patients with HM3 implanted within the Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy with HeartMate 3 (MOMENTUM 3) trial portfolio who underwent 820 concurrent procedures among which 466 (21.8%) were HM3+VP. VPs included 101 aortic, 61 mitral, 163 tricuspid; 85 patients had multiple VPs. Perioperative complications, major adverse events, and survival were analyzed. Patients who underwent HM3+VP had higher-acuity Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) profiles (1-2: 41% vs 31%) compared with no VPs (P <.05). The cardiopulmonary bypass time (124 vs 76 minutes; P <.0001) and hospital length of stay (20 vs 18 days; P <.0001) were longer in HM3+VP. A higher incidence of stroke (4.9% vs 2.4%), bleeding (33.9% vs 23.8%), and right heart failure (41.5% vs 29.6%) was noted in HM3+VP at 0 to 30 days (P <.01), with no difference in 30-day mortality (3.9% vs 3.3%) or 2-year survival (81.7% vs 80.8%). Analysis of individual VP showed no differences in survival compared to HM3 alone. No differences were noted among patients with either significant mitral (moderate or worse) or tricuspid (moderate or worse) regurgitation with or without corrective surgery. Concurrent VPs, commonly performed during LVAD implantation, are associated with increased morbidity during the index hospitalization, with no effect on short- and long-term survival. There is sufficient equipoise to consider a randomized trial on the benefit of commonly performed VPs (such as mitral or tricuspid regurgitation correction), during LVAD implantation. [Display omitted] [ABSTRACT FROM AUTHOR]

Background Paraplegia remains a devastating complication of thoracoabdominal aortic intervention. Metabolic stress induces expression of beta common receptor subunit of erythropoietin (EPO) receptor (βcR) to exert a neuroprotective effect in spinal cord ischemia reperfusion injury (SCIR). Diazoxide (DZ) has been shown to induce ischemic tolerance. We previously reported that DZ upregulated βcR expression and enhanced the neuroprotective effects of EPO through the upregulation of βcR. We hypothesize that βcR expression induced by DZ before ischemia amplifies the antiapoptotic effects of EPO in a murine model of SCIR. Methods Experimental groups included phosphate-buffered saline (PBS) pretreatment + PBS immediately before the operation, PBS+EPO, DZ+PBS, DZ+EPO, and sham. Spinal cord ischemia was induced by a 4-minute thoracic aortic cross-clamp. Functional scoring (Basso Mouse Score) was done at 12-hour intervals for 48 hours. Spinal cords were harvested for histologic analysis, and antiapoptotic factors (caspase 3, 8, and 9, B-cell lymphoma-2, and neuroglobin) were evaluated by Western blot analysis. Results The motor function of DZ+EPO group was significantly preserved compared with all other groups. The levels of cleaved caspase 8 and 3 in DZ+EPO were significantly lower than in the other groups. Mice treated with DZ+EPO had significantly fewer terminal deoxynucleotide transferase-mediated deoxy uridine triphosphate nick-end labeling–positive cells than other groups. Conclusions Optimized upregulation of βcR by DZ can increase the extrinsic antiapoptotic effects of EPO. Better understanding of this synergetic mechanism may serve to help prevent ischemic complications caused by aortic intervention. [ABSTRACT FROM AUTHOR]

Background Paraplegia remains the most feared complication of complex thoracoabdominal aortic intervention. Although erythropoietin (EPO) has demonstrated neuroprotective effects in spinal cord ischemia, it does not work until expression of the beta common receptor subunit of the EPO receptor (βcR) is induced by ischemia. We hypothesized that the βcR can be induced by diazoxide (DZ), amplifying the neuroprotective effects of EPO in spinal cord ischemia-reperfusion injury. Methods For the DZ time trial, adult male C57/BL6 mice received DZ (20 mg/kg) by oral gavage. Spinal cords were harvested after 0, 12, 24, 36, and 48 hours of administration. To evaluate optimal dosing, DZ was administered at 0, 5, 10, 20, and 40 mg/kg. The expression of βcR was assessed by Western blot analysis. Five groups were studied: PBS (pretreatment)+PBS (immediately before), PBS+EPO, DZ+PBS, DZ+EPO, and sham (without cross-clamping). Spinal cord ischemia was induced by 4 minutes of thoracic aortic cross-clamping. Functional scoring (Basso Mouse Score) was done at 12-hour intervals for 48 hours, and spinal cords were harvested for histological analysis. Results Western blot analysis demonstrated that optimal βcR up-regulation occurred at 36 hours after DZ administration, and the optimal DZ dosage for βcR induction was 20 mg/kg. Motor function at 48 hours after treatment was significantly better preserved in the DZ+EPO group compared with all other groups, and was significantly better preserved in the DZ only and EPO only groups compared with control (PBS+PBS). Conclusions Pharmacologic up-regulation of βcR with DZ can increase the efficacy of EPO in preventing spinal cord ischemia and reperfusion injury. Improved understanding of this synergetic mechanism may serve to further prevent ischemic complications for high-risk aortic intervention. [ABSTRACT FROM AUTHOR]

Background Paraplegia from spinal cord ischemia-reperfusion (SCIR) remains an elusive and devastating complication of complex aortic operations. Erythropoietin (EPO) attenuates this injury in models of SCIR. Upregulation of the EPO beta common receptor (βcR) is associated with reduced damage in models of neural injury. The purpose of this study was to examine whether EPO-mediated neuroprotection was dependent on βcR expression. We hypothesized that spinal cord neurons subjected to oxygen-glucose deprivation would mimic SCIR injury in aortic surgery and EPO treatment attenuates this injury in a βcR-dependent fashion. Methods Lentiviral vectors with βcR knockdown sequences were tested on neuron cell cultures. The virus with greatest βcR knockdown was selected. Spinal cord neurons from perinatal wild-type mice were harvested and cultured to maturity. They were treated with knockdown or nonsense virus and transduced cells were selected. Three groups (βcR knockdown virus, nonsense control virus, no virus control; n = 8 each) were subjected to 1 hour of oxygen-glucose deprivation. Viability was assessed. βcR expression was quantified by immunoblot. Results EPO preserved neuronal viability after oxygen-glucose deprivation (0.82 ± 0.04 versus 0.61 ± 0.01; p < 0.01). Additionally, EPO-mediated neuron preservation was similar in the nonsense virus and control mice (0.82 ± 0.04 versus 0.80 ± 0.05; p = 0.77). EPO neuron preservation was lost in βcR knockdown mice compared with nonsense control mice (0.46 ± 0.03 versus 0.80 ± 0.05; p < 0.01). Conclusions EPO attenuates neuronal loss after oxygen-glucose deprivation in a βcR-dependent fashion. This receptor holds immense clinical promise as a target for pharmacotherapies treating spinal cord ischemic injury. [ABSTRACT FROM AUTHOR]

Objectives: This study was undertaken to identify a preferred dosing strategy for patients undergoing coronary artery bypass grafting or valve replacement procedures with cardiopulmonary bypass. Methods: Patients undergoing coronary artery bypass grafting, valve replacement surgery, or both were randomly assigned to receive either standard 1-g dosing with vancomycin before and after cardiopulmonary bypass or a single weight-based 20-mg/kg dose before surgery. The primary outcome was the percentage of time plasma concentrations were greater than 15 μg/mL during cardiopulmonary bypass and at surgical closure. Secondary outcomes included concentration of vancomycin in endothoracic tissue after vancomycin infusion, average time patients had vancomycin concentrations greater than 15 μg/mL, and vancomycin plasma and tissue pharmacokinetic parameters. Results: Baseline characteristics were similar between the study dosing group (n = 10) and the standard dosing group (n = 10). From postinfusion to end of bypass, the median percentage of time vancomycin concentrations remained greater than 15 μg/mL was 100% (interquartile range [IQR], 72.6%-100%) for weight-based dosing versus 43.7% (IQR, 28.7%-53.4%) for standard dosing (P = .0005). From postinfusion to surgical closure, the percentage of time vancomycin concentrations remained greater than 15 μg/mL was significantly higher in the weight-based group (100% [IQR, 58.3%-100%] vs 34.6% [IQR, 25.3%-41.6%]; P = .0005). Weight-based dosing increased calculated time with vancomycin concentrations greater than 15 μg/mL and resulted in higher endothoracic tissue vancomycin concentrations. Conclusions: Weight-based vancomycin dosing before coronary artery bypass grafting or valve replacement results in vancomycin concentrations greater than 15 μg/mL consistently more than does standard 1-g dosing. [Copyright &y& Elsevier]

Background: Paraplegia remains a devastating complication of thoracoabdominal aortic procedures resulting from spinal cord ischemia and reperfusion injury (SCIR). Pharmacologic interventions have not proven efficacious in attenuating this injury, with poor understanding of the underlying mechanisms. The resident macrophages, or microglia in the spinal cord, may play a significant role in SCIR. The macrolide antibiotic, minocycline, has been shown in stroke models to inhibit microglial activation. This study hypothesized that microglial inhibition by minocycline after SCIR will attenuate injury with preservation of motor function. Methods: Mature male C57Bl/6 mice underwent 4 minutes of thoracic aortic occlusion with reperfusion. Mice receiving minocycline 30 minutes before ischemia and daily thereafter (90 mg/kg and 45 mg/kg, respectively) were compared with mice receiving vehicle controls. Hind-limb motor function was measured at 12-hour intervals, with spinal cord harvest for histologic and immunologic comparison at 60 hours. Results: Minocycline treatment significantly preserved hind limb motor function in all mice (n = 7) compared with complete paralysis in all untreated mice (n = 8), reaching significance from 24 hours of reperfusion through 60 hours. Immunofluorescent staining for Iba-1 revealed significant inhibition of microglial activation by minocycline treatment. Vehicle control sections demonstrated a greater degree of apoptosis compared with minocycline-treated spinal cord sections. Conclusions: Minocycline limits microglial activation, paralleling functional preservation after aortic cross-clamping. These data suggest functional microglia contribute to reperfusion injury after spinal cord ischemia. The effects of minocycline demonstrate a potential pharmacological therapy as well as demonstrating a potential cellular target in preventing paraplegia after aortic intervention. [ABSTRACT FROM AUTHOR]

Objective: Irradiation of the chest or chest wall has been shown to cause calcific aortic stenosis. However, the mechanisms are unknown. Aortic valve interstitial cells have been implicated in the pathogenesis of aortic stenosis; they have been shown to change from the phenotype of a myofibroblast to an osteoblastlike cell. We therefore hypothesized that irradiation of human aortic valve interstitial cells induces an osteogenic phenotype. In isolated human aortic valve interstitial cells, our purpose was to determine the effect of irradiation on the production of osteogenic factors: (1) bone morphogenetic protein 2, (2) osteopontin, (3) alkaline phosphatase, and (4) the transcription factor Runx2. Methods: Human aortic valve interstitial cells were isolated from normal aortic valves obtained from explanted hearts of patients undergoing cardiac transplantation (n = 4) and were grown in culture. The cells were grown to confluence, irradiated with 10 Gy using a cesium-137 irradiator, and then lysed 24 hours after irradiation. Cell lysates were analyzed via immunoblot and densitometry for bone morphogenetic protein 2, osteopontin, alkaline phosphatase, and Runx2. Statistical analysis was performed using analysis of variance, with P < .05 indicating significance. Results: Irradiation induced an osteogenic phenotype in human aortic valve interstitial cells. Irradiation induced a 2-fold increase in bone morphogenetic protein 2, a 7-fold increase in osteopontin, a 3-fold increase in alkaline phosphatase, and a 2-fold increase in Runx2. Conclusions: Radiation induces an osteogenic phenotype in human aortic valve interstitial cells. The irradiated cells had a significantly increased expression of the osteogenic factors bone morphogenetic protein 2, osteopontin, alkaline phosphatase, and Runx2. These data offer mechanistic insight into the pathogenesis of radiation-induced valvular heart disease. [Copyright &y& Elsevier]

Background: Patients requiring biventricular assist device (BiVAD) for mechanical circulatory support (MCS) have substantially worse outcomes than patients requiring left VAD (LVAD) support only. Patient-specific risk factors have yet to be consistently identified in a large, multicenter registry, which may underlie the poorer outcomes for BiVAD patients. The Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) is a registry of U.S. Food and Drug Administration–approved durable MCS devices used for bridge-to-transplantation, destination therapy, or recovery. The purposes of this study were to 1) identify the underlying pre-implant characteristics of the population requiring BiVAD support that contribute to reduced survival, and 2) identify differences in postoperative outcomes with respect to adverse events compared with patients supported with LVAD alone. Methods: From June 2006 to September 2009, 1,646 patients were entered into the INTERMACS database in which adverse events and outcomes were recorded for primary implants with LVAD or BiVAD. Competing outcomes methodology was used to estimate the time-related probability of death, transplant, or recovery. Overall survival for all groups was analyzed with Kaplan-Meier methods and Cox proportional regression analysis. Results: The distribution of primary device implants included 1,440 LVADs and 206 BiVADs. BiVAD patients presented with a lower INTERMACS profile 93% in INTERMACS 1 or 2, compared with 73% for LVAD patients (p < 0.001). Survival at 6 months was 86% for LVADs and 56% for BiVADs (p < .0001). Adverse event rates, expressed as episodes/100 patient-months for the BiVAD group compared with LVAD, were significantly higher for infection (33.2 vs 14.3), bleeding (71.6 vs 15.5), neurologic events (7.9 vs 2.6), and for device failure (4.9 vs 2.0). Conclusions: Patients requiring BiVAD support at the time of durable MCS implant are more critically ill at the time of MCS implant. BiVAD patients experience worse survival than patients supported with LVAD alone and higher rates of serious adverse events. Characteristics of the population present at the time of BiVAD implant likely influence post-implant MCS outcomes. [Copyright &y& Elsevier]

Background: A donor lung shortage prevents patients from receiving life-saving transplants. Ex-vivo lung perfusion (EVLP) is a viable means of expanding the donor pool by evaluating and potentially improving donor lung function. The metabolic and inflammatory effects of EVLP on human lung tissue are currently unknown. We sought to establish representative cytokine expression in human donor lungs meeting acceptable lung transplant criteria after prolonged normothermic EVLP. Methods: Seven single human lungs not meeting traditional transplantation criteria for various reasons underwent normothermic EVLP. Lungs were perfused with deoxygenated colloid, rewarmed, and ventilated per standard protocol. Lung function was evaluated every hour. Biopsies were taken at 1, 6, and 12 hours. Inflammatory cytokines were quantitatively measured using a human cytokine magnetic bead-based multiplex assay. Results: All lungs met traditional transplant criteria after EVLP. The partial pressure of arterial oxygen and physiologic lung function significantly improved (p < 0.05). No pulmonary edema was formed, and histology demonstrated no evidence of acute lung injury. Interleukin (IL)-6, IL-8, granulocyte colony-stimulating factor, and monocyte chemotactic protein-1 were upregulated, while granulocyte macrophage colony-stimulating factor was downregulated during EVLP (p < 0.05). IL-1β, IL-4, IL-7, IL-12, interferon-γ, macrophage inflammatory protein-1β, and tumor necrosis factor-α were detectable and unchanged. Conclusions: Ex-vivo lung perfusion demonstrates the ability to improve oxygenation and physiologic lung function in donor lungs unacceptable for transplantation without injury to the lung. We establish here a cytokine expression profile in human lungs undergoing normothermic EVLP. These data can be used in the future to explore novel targeted therapies for ischemia-reperfusion injury. [ABSTRACT FROM AUTHOR]

Objective: Aortic stenosis is an inflammatory disease, associated with increased tissue levels of interleukin-1 beta. We hypothesized that the antagonist of interleukin-1 beta, interleukin-1 receptor antagonist, is deficient in aortic valves and that its production by aortic valve interstitial cells is less in cells from stenotic valves than from controls. Methods: Valve leaflets from stenotic aortic valves (n = 6) and from valves from hearts explanted at the time of cardiac transplantation (n = 6) were studied by immunostaining for interleukin-1 receptor antagonist. Aortic valve interstitial cells were isolated from valves, and receptor antagonist levels were determined from cell lysates (enzyme-linked immunosorbent assay). Osteogenic phenotype changes in valve cells stimulated by toll-like receptors 2 and 4 were determined by immunoblotting for bone morphogenetic protein-2 after treatment with and without interleukin-1 receptor antagonist (100 μg/mL). Statistics were by analysis of variance. Results: Interleukin-1 receptor antagonist was abundant in nonstenotic aortic valve leaflets and virtually absent in leaflets from stenotic valves. Aortic valve interstitial cells from grossly normal leaflets produced significantly more receptor antagonist at baseline and in response to toll-like receptor 2 and 4 stimulation, than did cells from diseased valves (P < 0.05). Interleukin-1 receptor antagonist was able to significantly attenuate toll-like receptor 2, but not toll-like receptor 4, stimulated bone morphogenetic protein-2 production in aortic valve interstitial cells (P < .05). Conclusions: Interleukin-1 receptor antagonist–mediated mechanisms of anti-inflammation are dysfunctional in stenotic valves. We conclude that such impaired mechanisms of anti-inflammation may contribute to the pathogenesis of aortic stenosis. [ABSTRACT FROM AUTHOR]

Background: Paraplegia remains a devastating complication for patients undergoing thoracic aortic procedures. Although surgical adjuncts have evolved to reduce the risk of paraplegia, no pharmacologic therapies have proven efficacious in attenuating spinal cord ischemia–reperfusion injury. Effects of erythropoietin in spinal cord ischemia–reperfusion injury, however, have not yet been elucidated. We hypothesized that pretreatment with erythropoietin would attenuate functional and cytoarchitectural spinal cord injury related to high-risk aortic procedures. Methods: Adult male mice were subjected to ischemia–reperfusion. Aortic arch and proximal left subclavian arteries were clamped for 5 minutes; animals were observed for 48 hours. Neurologic scores of hind limb function were assessed every 12 hours. Experimental groups consisted of treatment with erythropoietin 4 hours before crossclamping (n = 7), ischemic controls (n = 7), and sham ischemia (operation without crossclamping, n = 6). Thoracolumbar sections of spinal cord were removed after 48 hours and preserved for cytoarchitectural analysis. Results: Mice pretreated with erythropoietin exhibited significant preservation of hind limb motor function. All mice without pretreatment were paralyzed at 48 hours. Mice with erythropoietin pretreatment had improved motor function; 3 had no measurable neurologic deficit at 48 hours. Histologic analysis in mice treated with erythropoietin showed markedly reduced neuronal cell injury. Conclusions: Erythropoeitin preserves both function and histologic appearance in mice undergoing spinal cord ischemia–reperfusion. With further elucidation of mechanisms of protection and optimal administration, erythropoietin could become an important adjunct in reducing the incidence and severity of spinal cord injury related to aortic interventions. [Copyright &y& Elsevier]

Objective: Selected patients appear to benefit from off-pump coronary artery bypass compared with conventional coronary artery bypass with cardiopulmonary bypass. It is unknown whether elderly patients undergoing isolated coronary artery bypass grafting operations derive any benefit when performed off-pump. We hypothesized that off-pump coronary bypass offers a greater operative benefit to elderly patients when compared with conventional coronary artery bypass. Methods: A total of 1993 elderly patients (age ≥ 80 years) underwent isolated, primary coronary artery bypass graft operations at 16 different statewide centers from 2003 to 2008. Patients were stratified into 2 groups: conven-tional coronary artery bypass (n = 1589, age = 82.5 ± 2.4 years) and off-pump bypass (n = 404, age = 83.0 ± 2.4 years). Preoperative risk, intraoperative findings, postoperative complications, and costs were evaluated. Results: Patients undergoing off-pump bypass grafting were marginally older (P = .001) and had higher rates of preoperative atrial fibrillation (14.6% vs 10.0%; P = .01) and New York Heart Association class IV heart failure (29.7% vs 21.1%; P < .001) than did those having conventional coronary bypass grafting. Other patient risk factors and operative variables, including Society of Thoracic Surgeons predicted risk of mortality, were similar in both groups (P = .15). Compared with off-pump bypass, conventional coronary bypass incurred higher blood transfusion rates (2.0 ± 1.7 units vs 1.6 ± 1.9 units; P = .05) as well as more postoperative atrial fibrillation (28.4% vs 21.5%; P = .003), prolonged ventilation (14.7% vs 11.4%; P = .05), and major complications (20.1% vs 15.6%; P = .04). Importantly, postoperative stroke (2.6% vs 1.7%; P = .21), renal failure (8.1% vs 6.2%; P = .12), and postoperative length of stay (P = .41) were no different between groups. Despite more complications in patients having conventional bypass, operative mortality (P = .53) and hospital costs (P = .43) were similar to those of patients having off-pump procedures. Conclusions: Performance of coronary artery bypass grafting among octogenarian patients is safe and effective. Off-pump coronary artery bypass confers shorter postoperative ventilation but equivalent mortality to conventional coronary artery bypass. Off-pump coronary artery bypass was associated with a reduction in the composite incidence of major complications in unadjusted and adjusted analyses and should be considered an acceptable alternative to conventional bypass for myocardial revascularization in elderly patients. [Copyright &y& Elsevier]

Abstract: Background: The left ventricular assist device (LVAD) is a therapy for patients with end-stage heart failure, many of whom have a preexisting implantable cardioverter-defibrillator (ICD). We investigated whether the implantation of a LVAD affects ICD function. Methods and Results: Patients implanted with a LVAD between September 2000 and February 2009 were studied. Right ventricular (RV), right atrial, and left ventricular lead impedance, sensing, and capture thresholds were recorded before and after LVAD placement and subsequent lead-related interventions were noted. Of the 61 patients receiving a LVAD, data were collected from 30 patients who had preexisting ICDs. Significant pre-post differences were noted for all RV lead parameters: sensing amplitude decreased from 9.2±3.1 to 5.7±3.6 millivolts (P < .001); impedance decreased from 479±118 to 418±94 ohms (P =.008); and threshold increased from 4.3±6.7 to 11.0±16.8 microjoules (P =.021). As a result of alterations in lead parameters, 4 patients (13%) required lead revisions and 6 patients (20%) required ICD testing. Conclusions: Differences in ICD lead function were observed after LVAD placement resulting in clinically significant interventions. These data suggest that ICD interrogation be performed post-LVAD placement and that patients be counseled for the potential need for lead revisions and ICD testing when consented for a LVAD. [Copyright &y& Elsevier]

Objective: Left ventricular assist devices are increasingly used as a bridge to transplantation. It remains unclear whether the use of pretransplant left ventricular assist devices adversely affects short-term survival after cardiac transplantation. Methods: A retrospective review of 317 consecutive patients undergoing cardiac transplantation at an academic center between 1986 and 2006 was undertaken. Left ventricular assist devices were used pretransplant in 23 of these 317 patients, and 294 patients did not require left ventricular assist device support. Patients with a left ventricular assist device were supported with a Heartmate VE or Heartmate XVE (Thoratec Corp, Pleasanton, Calif). Kaplan–Meier survival estimates were compared between the left ventricular assist device group and the non-left ventricular assist device group using the log-rank test. In addition, occurrence of death was analyzed between the 2 groups with a chi-square analysis. The results are expressed as 1-year survival with 95% confidence intervals in parentheses. Results: The 1-year survival for all 317 patients was 0.86 (0.82–0.90). The patient survival for the group without a left ventricular assist device before cardiac transplant was 0.87 (0.83–0.90), and the survival for the group with a left ventricular assist device as bridge to transplantation was 0.83 (0.67–0.98; P = .77). For the deaths that occurred in all 317 patients, 19% of the patients without left ventricular assist devices died within 30 days of transplant, whereas 80% of the patients with left ventricular assist devices died within 30 days of transplant (P < .01). Conclusion: When used as a bridge to transplantation, left ventricular assist devices do not compromise 1-year survival after cardiac transplantation. Of the patients who die after transplantation, patients bridged with left ventricular assist devices are at higher risk for death within 30 days of transplant. These data suggest that left ventricular assist devices as a bridge to transplantation should be considered for appropriately selected patients awaiting cardiac transplantation. [Copyright &y& Elsevier]

Background: Calcific aortic stenosis may be an inflammatory disease with active bone formation in the valve leaflets rather than a disease of passive calcium deposition. Epidemiologic data demonstrating correlation of poor dental hygiene to atherosclerotic pathologies suggests that circulating bacterial products could be involved in the pathogenesis of aortic valve stenosis. We hypothesized that lipopolysaccharide (LPS) stimulation of human aortic valve interstitial cells (HAVICs) would induce inflammatory and osteogenic gene expression. Methods: The HAVICs were isolated from normal aortic valves obtained from explanted hearts during transplantation (n = 5) and grown in culture. Cells underwent 4 and 24 hours of LPS stimulation (LPS, 200 ng/mL) or β-glycerol phosphate treatment (BGP) (osteogenic media as positive control). Media was removed for interleukin (IL)-6 and IL-8 immunoassay. Ribonucleic acid was extracted for microarray analysis. Statistics were by analysis of variance with post-hoc analysis (p < 0.05). Results: The LPS stimulation induced the gene expression of proinflammatory cytokines, chemokines, and adhesion molecules. Protein level confirmation by immunoassay demonstrated 3.4-fold (± 0.35, p < 0.01) and 9.5-fold (± 1.5 p < 0.01) increase over control of IL-6 and IL-8, respectively. The LPS and BGP both induced critical mediators of osteogenesis including bone morphogenetic protein 2 and platelet-derived growth factor alpha. Conclusions: The LPS stimulation of HAVICs not only induces inflammatory mediators but also induces gene expression of osteogenic factors, similar to that induced by osteogenic media. Bacterial products stimulation, likely by toll-like receptor 4 and the innate immune system, may contribute to the pathogenesis of aortic valve stenosis. [Copyright &y& Elsevier]

Objective: The earliest response of esophageal mucosa to gastric reflux is the development of oxidative damage and inflammation. These processes contribute to the development of metaplasia known as Barrett''s esophagus, as well as the progression to malignancy. Secretory phospholipase A2 is a mediator of inflammation with levels that are increased in Barrett''s metaplasia and carcinoma when compared with levels in normal samples. Our goal is to determine the role of secretory phospholipase A2 in the development of reflux-associated changes in the esophageal mucosa. Methods: Secretory phospholipase A2–deficient mice (C57BL/6, n = 5) and mice known to express high levels of secretory phospholipase A2 (BALB/c, n = 5) underwent side-to-side surgical anastomosis of the first portion of the duodenum and gastroesophageal junction, allowing exposure of esophageal mucosa to duodenal and gastric contents duodeno-gastroesophageal anastomosis. Control animals (n = 5) of each strain underwent laparotomy with esophagotomy and repair. Tissue was frozen in embedding medium. Hematoxylin and eosin staining and Ki67 and secretory phospholipase A2 immunohistochemistry were used to evaluate esophageal tissue and its response to duodeno-gastroesophageal anastomosis. Results: Immunofluorescent staining confirmed the absence of secretory phospholipase A2 in C57BL/6 mice and its presence in BALB/c mice. Hematoxylin and eosin staining demonstrated significant thickening of the esophageal mucosa in response to gastroesophageal reflux in the presence of secretory phospholipase A2. Mice known to express high levels of secretory phospholipase A2 also demonstrated increased numbers of proliferating cells. Secretory phospholipase A2–deficient mice were immune to the early changes induced by mixed reflux. Conclusions: The presence of secretory phospholipase A2 appears necessary for early histologic changes produced by exposure of the esophagus to gastroduodenal contents. This enzyme is identified as a promising target for evaluation of mechanisms of carcinogenesis and chemoprevention of esophageal carcinoma. [Copyright &y& Elsevier]

Objective: Single-lung transplantation is an accepted treatment for end-stage lung disease caused by chronic obstructive pulmonary disease. A complication unique to single-lung transplantation for chronic obstructive pulmonary disease is graft dysfunction due to compression caused by native lung hyperinflation. We hypothesized that patients with functional compromise from native lung hyperinflation would benefit from native lung volume reduction surgery. Methods: The charts of all patients undergoing single-lung transplantation for chronic obstructive pulmonary disease were reviewed for lung volume reduction surgery of their native lung. Data regarding length of stay, surgical morbidity and mortality, overall survival, type of lung volume reduction surgery, and pulmonary function were recorded to evaluate the effect of lung volume reduction surgery. Results: Between February 1992 and May 2007, 206 single-lung transplantations were performed for chronic obstructive pulmonary disease. Ten (5%) patients had clinically significant graft compression from native lung hyperinflation. After excluding other causes for functional decline, these patients underwent a modified lung volume reduction surgery between 12 and 142 months after single-lung transplantation (mean, 50 months). Lung volume reduction surgery consisted of anatomic resection. Two (20%) of 10 patients died during their hospitalization. Of the remaining 8 patients, 7 (87.5%) have demonstrated functional improvement on the basis of forced expiratory volume in 1 second improving from 12% to 200% (mean improvement, 57%). Within 6 months of lung volume reduction surgery, mean 6-minute walk values improved significantly (866 to 1055 feet), whereas desaturation with exertion decreased significantly. Conclusions: Lung volume reduction surgery by means of formal lobectomy in patients with native lung hyperinflation undergoing single-lung transplantation and significant graft compression appears feasible. Additionally, improvements in forced expiratory volume in 1 second can be accomplished in nearly all properly selected patients. Lung volume reduction surgery should be considered in patients with decreasing graft function caused by graft compression from native lung hyperinflation. [Copyright &y& Elsevier]

Objectives: The appropriate index of prosthesis internal orifice size and its effect on operative mortality after aortic valve replacement are controversial. We examined the association between several relevant indices and patient size on operative mortality. Indices examined included projected in vivo effective orifice area and geometric orifice area, with patient size defined as body surface area. Methods: A review of the Society of Thoracic Surgeons National Cardiac Database (2000-2004) yielded 48,722 patients who had isolated aortic valve replacement. This analysis is based on the cohort of 42,310 patients with the 8 most prevalent valve types with manufacturer’s labeled sizes 19 mm through 29 mm. Multivariable logistic regression models were employed to determine the effects of body surface area, effective orifice area, geometric orifice area, and selected derived indices (eg, effective orifice area/body surface area) on risk-adjusted operative mortality. Results: In separate multivariable models, effective orifice area and geometric orifice area were both inversely correlated with operative mortality. However, an unanticipated finding was that with either effective orifice area or geometric orifice area held constant, body surface area was significantly and inversely correlated with operative mortality. When patients were stratified by effective orifice area, geometric orifice area, or manufacturer’s labeled valve size and type, elevations in body surface area were associated with a decrease rather than an increase in operative mortality. Conclusions: Prostheses with small geometric orifice area or small effective orifice area are associated with increased operative mortality after isolated aortic valve replacement. Even for valves with small effective orifice area, however, mortality decreases as body surface area increases. With respect to operative mortality, therefore, our results do not support using arbitrary cutoff values of effective orifice area/body surface area to determine the valve to utilize in a given patient. [Copyright &y& Elsevier]