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Background The relationship between low oxygen delivery (DO2) on cardiopulmonary bypass and morbidity and mortality following cardiac surgery remains unexamined. Methods We reviewed patients undergoing Society of Thoracic Surgeons index procedures from March 2019 to July 2020, coincident with implementation of a new electronic perfusion record that provides for continuous recording of DO2 and flow parameters. Continuous perfusion variables were analyzed using area-over-the-curve (AOC) calculations below predefined thresholds (DO2 24 hours, stroke, sternal wound infection, and reoperation). Results Eight hundred thirty-four patients were included; 42.7% (356) underwent isolated coronary artery bypass grafting (CABG), whereas 57.3% underwent nonisolated CABG (eg, valvular or combined CABG/valvular operations). DO2 24 hours (P = .04), an effect again most pronounced in nonisolated-CABG cases (P = .002), as well as acute kidney injury Conclusions Low DO2 on bypass may be associated with morbidity/mortality following cardiac surgery, particularly in patients undergoing nonisolated CABG. These results underscore the importance of goal-directed perfusion strategies.

BACKGROUND: We hypothesized that long-term clinical and echocardiographic recovery of the impaired ventricle from pressure (aortic stenosis [AS]) and volume (aortic regurgitation [AR]) overload would be different after aortic valve replacement (AVR). METHODS: We compared the results of AVR in patients with a preoperative ejection fraction (EF) of 0.35 or less due to AS, AR, or mixed disease. We constructed a mixed-effects model of EF and left ventricular (LV) end-diastolic diameter (LVEDD) to understand ventricular recovery over the short- (in-hospital), intermediate- (3–6 months), and longer- (>24 months) terms. We sought to identify factors associated with clinical and echocardiographic recovery using multivariable analysis. RESULTS: Between July 2011 and 2017, 136 patients with a preoperative EF of 0.35 or less and severe AS (n = 83), severe AR (n = 18), or mixed AS and AR (n = 35) underwent AVR. There were 2 (1.5%) early deaths in the AS group. Survival at 1, 2, and 5 years did not differ between groups. Baseline EF did not differ between the groups but improved with markedly different trajectory and time course in the AS, AR, and mixed groups over time. LVEDD regressed in all patient cohorts, following a different pattern for AS and AR. Baseline EF and LVEDD predicted the long-term fate of the LV but did not determine survival. We identify factors associated with long-term survival. CONCLUSIONS: The pattern of LV recovery appears to be early in AS and delayed in AR. Baseline clinical factors, rather than echocardiographic status of the LV, appear to determine late survival.

Aortic root replacement is a complex procedure. Recently, the KONECT RESILIA aortic valved conduit (Edwards Lifesciences, Irvine, CA), the first prefabricated biologic valved conduit available in the United States, was approved for use. Here, we report a series of 3 patients representing implantation of the novel Konect AVC. The conduit was implanted in both supraannular and intraannular positions, and the unique design of the sewing ring offers several advantages. The Konect AVC streamlines the process of root replacement and may represent an improvement in terms of ease of implantation and durability.

OBJECTIVES The purpose of this study was to evaluate the association between left ventricular (LV) dilation and outcomes following valve-sparing root reimplantation. METHODS Patients with an indexed LV internal diameter during systole of ≥2.0 cm/m2 were categorized as having LV dilation. Outcomes were postoperative aortic insufficiency (AI), reintervention and all-cause mortality. The cumulative incidence of each outcome was computed using the Kaplan–Meier estimator. Adjusted comparisons between strata were performed for each outcome using a Cox proportional-hazards model. Where possible, the competing risk of death was accounted for. Multilevel mixed-effects ordered logistic regression was performed for AI grade at follow-up. RESULTS There were 295 patients of whom 52 had LV dilation. Operative outcomes were excellent; there were no significant differences between groups. Patients with LV dilation demonstrated significant improvement in indexed LV internal diameter during systole overtime. There was no association between LV dilation and postoperative AI grade >2 [hazard ratio 0.88, 95% confidence interval (CI) 0.21–3.67, P = 0.89] or odds of increased AI grade overtime (odds ratio = 0.76, 95% CI 0.30–1.93, P = 0.57). There were no re-interventions among those with LV dilation. Adjusted mortality was significantly higher among those with LV dilation (hazard ratio 5.56, 95% CI 1.56–19.9); however, deaths were unrelated to aortic valve dilation. CONCLUSIONS LV dilation is not associated with poorer operative outcomes, postoperative AI or reintervention. It is associated with an increased risk of mortality, though not from valvular dysfunction. LV dilation should not deter valve-sparing root reimplantation when otherwise indicated.

Background Since the first reported use of prosthetic aortic grafts, infection has remained a feared complication. Pedicled omentum is the preferred flap in managing thoracic aortic graft infection (TAGI); however the literature is sparse. The authors present their experience with TAGI managed with pedicled omental flaps. Methods A single-institutional review from 2007 to 2018 was performed to analyze postoperative outcomes of omental flap reconstruction, performed by 2 surgeons, after a confirmed diagnosis of TAGI. The primary outcomes of overall complication rate, 30-day mortality, and in-hospital mortality were evaluated with univariate analysis. Results Twenty patients requiring omental flap reconstruction after TAGI met inclusion criteria. The patient cohort included 14 men and 6 women with a mean age of 60.6 ± 12.9 years and a mean Charlson comorbidity index of 3.3 ± 2.1. Nine patients (45%) received omental flap reconstruction at the time of incipient TAGI surgical management by the cardiothoracic surgery team, whereas 11 patients received delayed reconstruction (mean, 6.22 days [range, 1-27]). The most common complications were graft leak (20%) and pseudoaneurysm (25%), with only 1 patient developing recurrent infection. Overall 30-day mortality was 20%. Chronic obstructive pulmonary disease and delayed omental flap reconstruction were associated with 30-day mortality (P = .04). Four of 11 patients (36.4%) who received delayed omental flap reconstruction died within 30 days, whereas 0 of 9 patients (0%) in the immediate omental coverage group died within 30 days (P = .043). Conclusions High mortality rates associated with TAGI exemplify the challenges associated with this disease process and patient population. Pedicled omentum is a safe adjunct with promising results to the management of TAGI while significantly reducing the risk of reinfection.

The University of Pennsylvania classification system (Penn class) of acute type A aortic dissection (aTAAD) is used to evaluate the impact of malperfusion on surgical outcomes. The purpose of this analysis was to determine the validity of Penn class in a larger and more contemporary cohort and to compare its performance with other classification systems.This was a retrospective study of patients who underwent aTAAD repair at our institution from 1993 to 2020. Patients were assigned to Penn class on the basis of burden of preoperative malperfusion syndrome. The association of Penn class and 30-day mortality was evaluated by multivariable regression. The discriminatory ability of Penn class for mortality was determined by a bootstrapped C statistic.There were 1192 patients, of whom 50% were assigned to Penn class A (no ischemia), 21% (253/1192) to class B (local ischemia), 14% (171/1192) to class C (generalized ischemia), and 14% (167/1192) to class B-C (combined ischemia). The incidence of mortality rose significantly with increasing Penn class from 5% (31/601) in class A to 35% (59/167) in class B-C (P.001). After adjustment, 30-day mortality increased significantly with class B (odds ratio [OR], 2.43; 95% CI, 1.38-4.27), class C (OR, 3.39; 95% CI, 1.90-6.03), and class B-C (OR, 13.08; 95% CI, 7.90-22.15) compared with class A. The C statistic was 0.77 (95% CI, 0.72-0.80) and was significantly higher than for models featuring alternative classification systems (P.05).Penn class provides excellent discrimination for 30-day mortality after repair of aTAAD.

In patients with preoperative atrial fibrillation (AF) undergoing aortic valve replacement, the addition of surgical ablation to surgical aortic valve replacement (SAVR-SA) is efficacious and a Class I guideline. We hypothesized that this subgroup may benefit from SAVR-SA compared to transcatheter aortic valve replacement (TAVR) alone.Medicare beneficiaries with persistent non-valvular AF who underwent SAVR-SA or TAVR alone between 2012 and 2018 were included. Patients with high-risk surgical comorbidities were excluded. Groups were matched using inverse probability weighting. The primary outcome was all-cause mortality. Secondary outcomes were stroke, transient ischemic attack, permanent pacemaker implantation, bleeding, rehospitalization for atrial arrhythmias, and rehospitalization for heart failure. Kaplan-Meier estimates and Cox proportional-hazards regression were used to compare outcomes. Outcomes were adjusted for variables with a standardized mean difference greater than 0.1.Of 439,492 patients who underwent aortic valve replacement, 2591 underwent SAVR-SA and 1494 underwent TAVR alone. Weighting resulted in adequately matched groups. Compared to TAVR alone, SAVR-SA was associated with a significant reduction in all-cause mortality (HR 0.65, 95% CI 0.53-0.79), permanent pacemaker implantation (HR 0.62, 95% CI 0.44-0.87), bleeding (HR 0.63, 95% CI 0.39-1.00), and rehospitalization for heart failure (HR 0.49 (0.36-0.65). There was no difference in the incidence of stroke (HR 1.07, 95% CI 0.74-1.54), transient ischemic attack (HR 1.05, 95% CI 0.75-1.47), or rehospitalization for atrial arrhythmia.Select patients with persistent non-valvular AF may benefit from SAVR-SA compared to TAVR alone.

General anesthesia (GA) is associated with inherent risks that can be avoided by the use of lesser invasive anesthetic strategies. We hypothesize that examine and compare the use of local or regional anesthesia (LRA) to that of GA in patients undergoing thoracic endovascular aortic repair (TEVAR).Patients undergoing TEVAR between 2010 and 2020 in the Vascular Quality Initiative were analyzed. Exclusion criteria included receipt of branched or physician-modified endografts and devices extending distally beyond zone 5. Patients were categorized as receiving LRA or GA. Center volume was reported by quartile according to annualized TEVAR volume, and operative outcomes were compared using appropriate frequentists tests. Univariable and multivariable regression models for anesthesia type and operative outcomes were created to compare unadjusted and adjusted rates of each outcome. Long-term survival was estimated using a Kaplan-Meier survival estimator, whereas adjusted survival analysis was performed using a Cox proportional hazards model.Of the 17,099 patients who underwent TEVAR, 7299 met the inclusion and exclusion criteria. Of these, 3.8% received LRA. There were no significant differences in the annual proportion of patients who received LRA from 2011 to 2020 (P = .49, χDespite a greater number of baseline comorbidities, patients undergoing TEVAR with LRA experienced shorter intensive care unit and postoperative lengths of stay, with similar operative outcomes and long-term survival compared with patients who received GA. Similar findings were found among the rupture cohort. LRA should be considered more frequently in select patients undergoing TEVAR.

BACKGROUND: Worse outcomes have been reported for women with type A acute aortic dissection (TAAD). We sought to determine sex-specific operative approaches and outcomes for TAAD in the current era. METHODS: The Interventional Cohort (IVC) of the International Registry of Acute Aortic Dissection (IRAD) database was queried to explore sex differences in presentation, operative approach, and outcomes. Multivariable logistic regression was performed to identify adjusted outcomes in relation to sex. RESULTS: Women constituted approximately one-third (34.3%) of the 2823 patients and were significantly older than men (65.4 vs 58.6 years, P < .001). Women were more likely to present with intramural hematoma, periaortic hematoma, or complete or partial false lumen thrombosis (all P < .05) and more commonly had hypotension or coma (P = .001). Men underwent a greater proportion of Bentall, complete arch, and elephant trunk procedures (all P < .01). In-hospital mortality during the study period was higher in women (16.7% vs 13.8%, P = .039). After adjustment, female sex trended towards higher in-hospital mortality overall (odds ratio, 1.40; P = .053) but not in the last decade of enrollment (odds ratio, 0.93; P = .807). Five-year mortality and reintervention rates were not significantly different between the sexes. CONCLUSIONS: In-hospital mortality remains higher among women with TAAD but demonstrates improvement in the last decade. Significant differences in presentation were noted in women, including older age, distinct imaging findings, and greater evidence of malperfusion. Although no distinctions in 5-year mortality or reintervention were observed, a tailored surgical approach should be considered to reduce sex disparities in early mortality rates for TAAD.

Background Ischemia-reperfusion injury is characterized by an increase in oxidative stress and leads to significant morbidity and death. The tyrosine kinase c-Abl is activated by oxidative stress and mediates processes that affect endothelial barrier function. We hypothesized treatment with the c-Abl inhibitor imatinib would be protective against ischemia-reperfusion injury in our ex vivo rabbit model. Methods Heart-lung blocs were harvested from rabbits and stored in cold in Perfadex (Vitrolife, Englewood, CO) for 18 hours. Blocs were reperfused for 2 hours in an ex vivo circuit with donor rabbit blood alone (untreated group, n = 7) or donor rabbit blood and 4 mg imatinib (treatment group, n = 10). Serial clinical variables measured every 15 minutes (arterial oxygen and carbon dioxide tension and mean pulmonary artery pressures) and biochemistry of tissue samples before and after reperfusion were assessed. Results Compared with untreated lungs, imatinib treatment improved physiologic parameters, including oxygen, carbon dioxide, and pulmonary artery pressures. Imatinib-treated lungs had less vascular barrier dysfunction as quantified by wet-to-dry weight ratios and bronchoalveolar lavage protein concentrations. Treated lungs showed less inflammation as measured by bronchoalveolar lavage myeloperoxidase assay, less mitochondrial reactive oxygen species production, and increased antioxidant catalase levels. Finally, imatinib protected lungs from DNA damage and p53 upregulation. Conclusions Imatinib treatment significantly improved the physiologic performance of reperfused lungs and biochemical indicators associated with reperfusion injury in this ex vivo model. Further study is necessary to elucidate the mechanism of tyrosine kinase inhibition in lungs exposed to ischemia and reperfusion.

In specific patients, early postoperative nutrition mitigates malnutrition-related morbidity and mortality. The goal of this study was to develop and validate a prediction score designed to stratify patients immediately after cardiac surgery according to risk for nutrition support (NS).We identified adult cardiac surgery patients at our institution in 2012 requiring postoperative NS, enteral or parenteral. Using multivariable logistic regression modeling, we developed a Johns Hopkins Hospital Nutrition Support (JHH NS) score from relative odds ratios generated by variables that independently predicted the need for NS. The JHH NS score was then prospectively validated using all patients undergoing cardiac surgery in 2015.Among 1,056 patients in the derivation cohort, 87 (8%) required postoperative NS. Seven variables were identified on multivariable analysis as independent predictors of NS need and were used to create the JHH NS score. Scores ranged from 0 to 36. Each 1-point increase in the JHH NS score was associated with a 20% increase in the risk of requiring NS (odds ratio 1.20, p 0.001). The c-statistic of the regression model for NS was 0.85. In all, 115 of 1,336 patients (8.6%) in the validation cohort required NS. Observed rates of NS in the validation group correlated positively with predicted rates (r = 0.89).The JHH NS score reliably stratified patients at risk for the need for postoperative NS. This easily calculable and highly predictive screening tool may expedite timing of initiation of NS in patients at high risk for not being able to physically take in adequate nutrition.

Background Dendrimer nanoparticle therapies represent promising new approaches to drug delivery, particularly in diseases associated with inflammatory injury. However, their application has not been fully explored in models of acute myocardial ischemia (MI) and reperfusion injury. Methods White male New Zealand rabbits underwent left thoracotomy with 30-minute temporary left anterior descending artery occlusion and MI confirmed by electrocardiography and histology (MI rabbits, n = 9), or left thoracotomy and pericardial opening for 30 minutes but no left anterior descending artery occlusion (control [C] rabbits, n = 9) rabbits. Following the 30-minute period, a dendrimer (generation 6 dendrimer conjugated to cyanine-5 fluorescent dye [G6-Cy5], 6.7 nm diameter) was administered intravenously and the chest closed in layers. Animals were sacrificed at 3 hours (3 MI, 3 C), 24 hours (3 MI, 3 C), or 48 hours (3 MI, 3 C) postsurgery. Results As compared to controls, MI rabbits had twofold G6-Cy5 uptake in the myocardial anterior wall as compared to the same region in nonischemic control rabbits at 24 hours postsurgery (6.01 ± 0.57 μg/g versus 2.85 ± 0.85 μg/g; p = 0.04). This trend was also present at 48 hours (6.38 ± 1.53 μg/g versus 3.95 ± 0.60 μg/g, p = 0.21) and was qualitatively evident on confocal microscopy. G6-Cy5 half-life in serum was approximately 12 hours, with 22% of the injected G6-Cy5 dose remaining at 48 hours. Conclusions This study demonstrates for the first time that dendrimer nanodevices selectively localize in ischemic as compared to healthy myocardium. This indicates that dendrimer nanodevices are promising agents to deliver drugs specifically to the ischemic myocardium to attenuate the injury. Subsequent studies will assess the efficacy of a dendrimer-drug conjugate in ameliorating reperfusion injury following MI.

The Society of Thoracic Surgeons (STS) database does not distinguish between a decline in creatinine clearance vs new hemodialysis (HD) when qualifying acute renal failure (ARF) after a cardiac operation. We hypothesized that patients requiring HD experience significantly greater postoperative morbidity and death.We included all patients who underwent STS index cardiac operations at our institution from 2008 to March 2015 and did not have preexisting renal failure (creatinine4.0 mg/dL or preoperative HD). We identified patients meeting STS criteria for ARF: threefold rise in serum creatinine, creatinine exceeding 4.0 mg/dL (non-HD ARF) with minimum rise of 0.5 mg/dL, or HD (ARF-HD). After propensity matching non-HD ARF and ARF-HD groups across 14 variables (including baseline glomerular filtration rate), we compared incidences of our primary outcome, death, and secondary outcomes, intensive care unit (ICU) and hospital length of stay (LOS), and discharge to a location other than home.Among 4,154 study patients, we identified 113 (2.7%) that experienced new-onset non-HD ARF (n = 57) or ARF-HD (n = 56) postoperatively. Propensity matching resulted in 51 well-matched pairs who experienced non-HD ARF or ARF-HD (all p0.10). Patients requiring HD suffered significantly greater operative mortality (67% vs 22%, p0.01), longer ICU LOS (326 vs 176 hours, p0.01), and greater postoperative hospital LOS (34 vs 17 days, p0.01). ARF-HD patients also demonstrated a trend toward higher rates of discharge to a location other than home (71% vs 45%, p = 0.08).After cardiac operations, patients who experienced ARF-HD experienced triple the mortality and double the ICU and postoperative hospital LOS compared with patients who experienced non-HD ARF.

Background Since the introduction of the Lung Allocation Score (LAS), the mean LAS has risen. Still, it remains uncertain whether mortality has improved in the most severely ill lung transplant recipients over this time period. Methods Using the United Network for Organ Sharing database, we identified 3,548 adult lung transplant recipients from May 4, 2005, to March 31, 2014, with a match-time LAS in the upper quartile (>75th%ile). We divided this population across three eras: 1 = May 4, 2005, to December 31, 2008 (n = 1,280); 2 = January 1, 2009, to December 31, 2011 (n = 1,266); and 3 = January 1, 2012, to March 31, 2014 (n = 1,002). Cox proportional hazards models were constructed for the primary outcomes of 30-day and 1-year mortality to assess the independent impact of the era of transplantation. Results The mean LAS at time of transplant for patients in the upper quartile in eras 1, 2, and 3 was 63, 73, and 79, respectively ( p p = 0.001) but not at 30 days (log-rank p = 0.152). After risk adjustment, lung transplantation in more recent eras was associated with improved mortality at both 30 days (era 3 hazard ratio [HR] = 0.50, 95% confidence interval [CI] 0.32% to 0.78%, p = 0.002) and 1 year (era 2 HR = 0.77, 95% CI 0.64% to 0.94%, p = 0.008; era 3 HR = 0.54, 95% CI 0.43% to 0.68%, p Conclusions Despite a progressively rising LAS, survival is improving among recipients with the highest LAS at the time of lung transplantation. This calls into question the notion of a maximum LAS beyond which lung transplantation becomes futile, a so-called LAS ceiling.

Concerns over prolonged allograft ischemia have limited the widespread adoption of long-distance organ procurement in heart transplantation (HT). We sought to assess whether donor distance from the center of transplantation independently affects mortality.We queried the United Network for Organ Sharing (UNOS) database for adults undergoing isolated HT from 2005 to 2012. Risk-adjusted Cox proportional hazards models were constructed for the primary outcomes of 30-day and 1-year mortality, and the independent impact of donor distance from transplantation center at the time of procurement was assessed.We included 14,588 heart transplant recipients. The mean distance from location of the donor heart to transplantation center was 184.4 ± 214.6 miles; 1,214 HTs (8.3%) occurred at the same location as the donor heart. Ischemic times were inversely related to the distance from the site of donor procurement to recipient transplantation. After risk adjustment, longer donor distances (in miles) were associated with a significantly lower risk of mortality at both 30 days (hazard ratio [HR] 0.9993, 95% confidence interval [CI]: 0.9988 to 0.9998, p 0.01) and 1 year (HR 0.9994, 95% CI: 0.9989 to 0.9999, p = 0.015). Risk-adjusted hazards for mortality were significantly reduced in recipients receiving hearts from more than 25 miles away. The hazard reduction was greatest in recipients receiving donor hearts from more than 500 miles away (1-year HR 0.64, p0.01; 30-day HR 0.47, p0.01).Longer distances between donor location and center of heart transplantation are associated with a reduced hazard for survival at 30 days and 1 year, despite greater ischemic times. Future studies are necessary to elucidate the protective factors surrounding long-distance heart donation.

Background The benefit of nanomedicine in mitigating acute lung injury (ALI) is currently unknown. Therefore, we introduced the generation IV polyamidoamine dendrimers with neutral surface property (dendrimer) into our established ex vivo animal model and sought to determine their biodistribution to define their cellular uptake profile and to evaluate their potential as a drug delivery candidate for the treatment of ischemia–reperfusion–induced ALI. Methods Eight rabbit heart–lung blocks were harvested and exposed to 18 h of cold ischemia. The heart–lung blocks were then reperfused with rabbit donor blood. Dendrimer was conjugated to fluorescein isothiocyanate (D-FITC) for localization and quantification studies. D-FITC (30 mg or 150 mg) was injected into the bypass circuit and baseline, 1- and 2-h tissue samples were obtained to determine percent uptake. Low (10×) and high (40×) magnification images were obtained using confocal microscopy to confirm the accumulation and to determine the cellular targets of the dendrimer. Results Four heart–lung blocks were exposed to 30 mg and four to 150 mg of D-FITC. After adjusting for dry weight, the mean uptake in the 30 and 150 mg samples after 2 h of reperfusion were 0.79 ± 0.16% and 0.39 ± 0.22% of perfused doses, respectively. Confocal imaging demonstrated dendrimer uptake in epithelial cells and macrophages. Conclusions Fluorescently tagged dendrimers demonstrated injury-dependent tissue accumulation in a variety of different cell types. This unique approach will allow conjugation to and delivery of multiple agents with the potential of mitigating ALI injury while avoiding systemic toxicity.

Hypothermic circulatory arrest (HCA) provides neuroprotection during cardiac surgery but entails an ischemic period that can lead to excitotoxicity, neuroinflammation, and subsequent neurologic injury. Hydroxyl polyamidoamine (PAMAM) dendrimers target activated microglia and damaged neurons in the injured brain, and deliver therapeutics in small and large animal models. We investigated the effect of dendrimer size on brain uptake and explored the pharmacokinetics in a clinically-relevant canine model of HCA-induced brain injury. Generation 6 (G6, ~6.7 nm) dendrimers showed extended blood circulation times and increased accumulation in the injured brain compared to generation 4 dendrimers (G4, ~4.3 nm), which were undetectable in the brain by 48 hrs after final administration. High levels of G6 dendrimers were found in cerebrospinal fluid (CSF) of injured animals with a CSF/serum ratio of ~20% at peak, a ratio higher than that of many neurologic pharmacotherapies already in clinical use. brain penetration (measured by drug CSF/serum level) of G6 dendrimers correlated with the severity of neuroinflammation observed. G6 dendrimers also showed decreased renal clearance rate, slightly increased liver and spleen uptake compared to G4 dendrimers. These results, in a large animal model, may offer insights into the potential clinical translation of dendrimers.

The purpose of this study was to develop and validate a risk score for readmissions after cardiac operations.Adults surviving to discharge after cardiac operations at a single institution from 2008 to 2013 were randomly divided 3:1 into training and validation cohorts. The primary outcome was readmission within 30 days of discharge. A multivariable model was constructed in the training cohort incorporating variables associated with 30-day readmission in univariate logistic regression. Points were assigned to predictors in the multivariable model proportional to their odds ratios.Among 5,193 patients undergoing cardiac operations and surviving to discharge, the 30-day readmission rate was 10.3% (n = 537). The most common reasons for readmission were volume overload (24%; n = 131) and infection (21%; n = 113). The risk score incorporated 5 multivariable predictors and was out of 20 possible points. The predicted rate of 30-day readmission based on the training cohort ranged from 5.9% (score = 0) to 54.7% (score = 20). Patients were categorized as low (score = 0; readmission 5.7%), moderate (score 1-7; readmission 11.0%), and high risk (score7; readmission 24.2%) (p0.001). Thirty-day readmission rates based on these score categories were similar in the validation cohort (low 6.4%, moderate 11.0%, high 17.4%; p0.001). There was a robust correlation between predicted rates of readmission in the training cohort based on the composite risk score and actual rates of readmission in the validation cohort (r = 0.95; p0.001).We developed and validated a risk score for readmission after cardiac operations that may have utility in targeting interventions and modifying risk factors in high-risk populations.

Background The utilization of multiorgan transplantation in cardiac transplantation has steadily increased over the past several years. We sought to characterize the trends and outcomes in simultaneous heart and other organ transplantation compared with heart transplantation alone. Methods The United Network for Organ Sharing database was queried for all adult patients (age ≥ 18 y) who underwent isolated heart transplantation or simultaneous heart-lung or heart-kidney transplantation from 1987-2016. Patients were stratified into 3 equal time intervals. Demographics and postoperative outcomes were compared. Results A total of 58,060 patients were identified with a distribution based on era. Dual organ recipients had more factors associated with increased operative risk including higher rates of diabetes, pulmonary hypertension, intensive care unit admissions, and dialysis prior to transplantation. Heart-lung and heart-kidney recipients had decreased 1-year survival compared with isolated heart recipients from 2007-2016. However, heart-kidney recipients had significantly increased 5-year post-transplantation survival compared with isolated heart recipients with impaired renal function. For isolated heart transplants and heart-lung transplants, 5-year survival rates improved over time, whereas 5-year survival for heart-kidney recipients did not improve with time. Conclusions We found a significantly increased 5-year survival rate for heart-kidney transplant recipients compared with isolated heart transplant recipients with renal impairment. Lack of improvement in 5-year postoperative outcomes for heart-kidney recipients in the setting of higher-risk pretransplant clinical characteristics suggests decreased selectivity regarding heart-kidney recipients. Continued scrutiny and evaluation of postoperative outcomes are required to ensure just and appropriate utilization of organs.

Background Neurocognitive dysfunction and injury remain problematic after cardiac procedures requiring hypothermic circulatory arrest (HCA). Due to poor blood-brain barrier penetrance and toxicities associated with systemic drug therapies, clinical success has been elusive. Accordingly, we explored targeted dendrimer (a nanoparticle) drug therapies in our well-established canine model of HCA to characterize the biodistribution and cellular localization of these nanoparticles in areas of known neuronal apoptosis and necrosis. Methods Class A, 27- to 30-kg male hounds were administered an initial intravenous bolus (10% of the total dose [200 mg]) of generation-six polyamidoamine dendrimer (6.7 nm) labeled with cyanine 5, and cardiopulmonary bypass with peripheral cannulation was initiated. After 90 minutes of HCA, 70% of the total dose was infused over a 6-hour period. The final 20% of the total dose was given 24 hours post-HCA. The brain was harvested 48 hours later (72 hours post-HCA) and analyzed for dendrimer 6-cyanine 5 biodistribution. Results The dorsal hippocampus demonstrated the highest brain accumulation of dendrimer 6-cyanine 5, which closely corresponds to the distribution of apoptotic neurons evident with histologic staining and on confocal imaging. In injured brain regions, dendrimer traversed the blood-brain barrier and localized within the target cells (injured neurons and microglia). Conclusions These findings have exciting implications for the future development of novel therapeutics to mitigate neurocognitive deficits in this group of patients.

The purpose of this study was to derive and validate a risk score for pneumonia (PNA) after cardiac surgery.Adults undergoing cardiac surgery between 2005 and 2012 were identified in a single-institution database. The primary outcome was postoperative PNA. Patients were randomly assigned to training and validation sets in a 3:1 ratio. A multivariable model was constructed incorporating univariate pre- and intraoperative predictors of PNA in the training set. Points were assigned to significant risk factors in the multivariable model based on their associated regression coefficients.A total of 6222 patients were included. The overall rate of postoperative PNA was 4.5% (n = 282). A 33-point score incorporating 6 risk factors (age, chronic lung disease, peripheral vascular disease, cardiopulmonary bypass time, intraoperative red blood cell transfusion, and pre- or intraoperative intra-aortic balloon pump) was generated. The model used to generate the score in the training set was robust in predicting PNA (c = 0.72, P.001). Predicted rates of PNA increased exponentially with increasing risk score, ranging from 1.2% (score = 0) to 59% (score = 33). There was significant correlation between predicted rates of PNA based on the training cohort and actual rates of pneumonia in the validation cohort in weighted regression analysis (r = 0.74, P.001). The composite score outperformed the STS prolonged ventilation model in predicting PNA in the validation cohort (c-index 0.76 vs 0.71, respectively).This 33-point risk score is strongly predictive of postoperative PNA after cardiac surgery. The composite score has utility in tailoring perioperative management and in targeting diagnostic and preventative interventions.

Objectives The aim of this study was to develop a risk index specific to patients on mechanical circulatory support that accurately predicts 1-year mortality after orthotopic heart transplantation using the United Network for Organ Sharing database. Background Few clinical tools are available to aid in the decision between continuing long-term device support and performing transplantation in patients bridging with mechanical circulatory support. Methods Using a prospectively collected, open cohort, 6,036 patients receiving mechanical circulatory support who underwent orthotopic heart transplantation between 2000 and 2013 were evaluated and randomly separated into derivation (80%) and validation (20%) groups. Multivariate logistic regression models were constructed using variables that improved the explanatory power of the model, which was determined using multiple methods. Points for a simple additive risk index were apportioned on the basis of relative effect on odds of 1-year mortality. Results A 75-point scoring system was created from 9 recipient and 4 donor variables. The average score in the validation cohort was 14.4 ± 7.7, and scores ranged from 0 to 57; these values were similar to those in the derivation cohort. Each 1-point increase predicted an 8.3% increase in the odds of 1-year mortality (odds ratio: 1.08; 95% confidence interval: 1.06 to 1.11). Low (0 to 10), intermediate (11 to 20), and high (>20) risk score cohorts were created, with predicted average 1-year mortalities of 8.6%, 12.8%, and 31%, respectively, in the validation cohort. Conclusions The investigators present a novel, internally cross-validated risk index that accurately predicts mortality in bridge-to-transplantation patients.

Prophylactic aortic root replacement improves survival in patients with Marfan syndrome with aortic root aneurysms, but the optimal procedure remains undefined.Adult patients with Marfan syndrome who had Bentall or aortic valve-sparing root replacement (VSRR) procedures between 1997 and 2013 were identified. Comprehensive follow-up information was obtained from hospital charts and telephone contact.One hundred sixty-five adult patients with Marfan syndrome (aged20 years) had either VSRR (n = 98; 69 reimplantation, 29 remodeling) or Bentall (n = 67) procedures. Patients undergoing Bentall procedure were older (median, 37 vs 36 years; P = .03), had larger median preoperative sinus diameter (5.5 cm vs 5.0 cm; P = .003), more aortic dissections (25.4% vs 4.1%; P.001), higher incidence of moderate or severe aortic insufficiency (49.3% vs 14.4%; P.001) and more urgent or emergent operations (24.6% vs 3.3%; P.001). There were no hospital deaths and 9 late deaths in more than 17 years of follow-up (median, 7.8 deaths). Ten-year survival was 90.5% in patients undergoing Bentall procedure and 96.3% in patients undergoing VSRR (P = .10). Multivariable analysis revealed that VSRR was associated with fewer thromboembolic or hemorrhagic events (hazard ratio, 0.16; 95% confidence interval, 0.03-0.85; P = .03). There was no independent difference in long-term survival, freedom from reoperation, or freedom from endocarditis between the 2 procedures.After prophylactic root replacement in patients with Marfan syndrome, patients undergoing Bentall and valve-sparing procedures have similar late survival, freedom from root reoperation, and freedom from endocarditis. However, valve-sparing procedures result in significantly fewer thromboembolic and hemorrhagic events.

Left ventricular assist devices (LVADs) are the most common mode of circulatory support for patients awaiting heart transplantation. Unfortunately, a fraction of these patients require pump exchange during their course for pump-related adverse events. This study examined whether LVAD exchanges affect posttransplantation outcomes.This study focused on adult patients in the Organ Procurement and Transplantation Network database who were bridged to transplant with a LVAD implanted between 2007 and 2017. Patients who underwent LVAD exchange were compared with those supported with a single device. The primary end point was all-cause mortality at 1, 2, and 5 years after transplantation. The impact of device exchange on risk-adjusted outcomes was examined using Cox proportional hazards models.Among 8239 patients who met the inclusion criteria, there were 611 pump exchanges in 560 patients (7% of recipients). The pump exchange rate was 6.24 events per 100 patient-years. Survival at 5 years was lower for those who underwent LVAD exchange (69.4% vs 77.5%, log-rank P = .027). This finding was similar for risk-adjusted 5-year mortality (hazard ratio, 1.36; 95% confidence interval, 1.11 to 1.67; P = .003). Subgroup analysis revealed lower 5-year survival for female recipients who underwent LVAD exchange (55.4% vs 79.7%, log-rank P.001). The interaction between female sex and LVAD exchange was associated with increased risk-adjusted 5-year mortality (hazard ratio, 1.65; 95% confidence interval, 1.05 to 2.59; P = .030).Recipients who underwent pump exchange while awaiting heart transplantation had a higher mortality compared with those on a primary device. Subgroup analysis revealed a marked increase in mortality of female recipients who experienced LVAD exchange.

The effect of size mismatch between donor and recipient in pediatric lung transplantation (PLTx) is currently unknown. Previous studies in adults have suggested that oversized allografts are associated with improved outcomes after lung transplantation. We investigated this relationship to quantify its effect on posttransplant outcomes in children.The United Network of Organ Sharing database was queried for preadolescent (age13 years) patients undergoing PLTx. Donor-to-recipient height, weight, and predictive total lung capacity (pTLC; ages 4 to 13; pTLC = 0.160 x exp[0.021 x height]) ratios were calculated. Exploratory analysis was performed to identify disjoint intervals at which survival was statistically different. Patients were categorized as well-matched, undersized, or oversized. Multivariate Cox proportional hazard regression modeling assessed the adjusted effect of mismatching on mortality. Survival analysis was performed using the Kaplan-Meier method.The analysis included 540 children. One-year mortality was higher with a height mismatch of 5% or less (hazard ratio [HR], 2.97; p = 0.001) and above 5% (HR, 2.22; p = 0.009). Similarly, 1-year mortality was worse with weight mismatch of 10% or less (HR, 1.99; p = 0.035) and above 10% (HR, 2.04; p = 0.028). On unadjusted analysis, a pTLC ratio of less than 0.9 was associated with worse survival (p = 0.017). This finding persisted after multivariate risk adjustment (HR, 2.93; p = 0.02). Contrary to findings in adults, an oversized allograft (pTLC ratio1.1) was not associated with improved survival (HR, 1.95; p = 0.147).In preadolescent children undergoing PLTx, size mismatching is associated with increased death. Our findings differ from studies in adults, which demonstrated improved survival associated with oversized allografts. Accordingly, well-matched allografts should be prioritized when assessing donor-recipient pairs for transplantation.

Acute kidney injury (AKI) continues to complicate cardiac operations. We sought to determine whether nadir oxygen delivery (DO2) on cardiopulmonary bypass (CPB) was a risk factor for AKI while also accounting for other postoperative factors.Using propensity scoring, we matched 85 patients who developed AKI after cardiac operations on CPB with 85 control patients who did not. We analyzed the following variables through midnight on postoperative day 1 (POD1): DO2, antibiotics, blood products and vasopressors (intraoperatively and postoperatively), and hemodynamic variables.Univariable analysis revealed AKI patients had lower nadir DO2 on CPB (208 vs 230 mL O2/min/m(2) body surface area, p = 0.03), lower intensive care unit admission blood pressure gradient across the kidney (mean arterial pressure minus central venous pressure; 60 vs 68 mm Hg; p0.001), a greater proportion of patients with mean arterial pressure of less than 60 mm Hg for more than 15 minutes in the postoperative period (70% vs 42%, p0.001), a greater chance of having a cardiac index of less than 2.2 (74% vs 49%, p = 0.02), and greater total vasopressor use through the end of POD1 (5.2 vs 2.3 mg, p = 0.002). On multivariable analysis, predictors of AKI were a DO2 on CPB of less than 225 mL O2/min/m(2) (odds ratio, 2.46; 95% confidence interval, 1.21 to 5.03; p = 0.01) and postoperative mean arterial pressure of less than 60 mm Hg for more than 15 minutes (odds ratio, 3.96; 95% confidence interval, 1.92 to 8.20; p0.001). An average postoperative pressor dose greater than 0.03 μg/kg/min did not reach significance (odds ratio, 1.98; 95% confidence interval, 0.95 to 4.11; p = 0.07).Postoperative hypotension on POD0 or POD1 and low DO2 on CPB both independently increase the AKI risk in cardiac surgical patients.

The aim of this study was to determine whether institutional volume influenced the effect of postoperative complications on short-term and long-term survival after orthotopic heart transplantation (OHT).The United Network for Organ Sharing database was queried for adult patients (aged ≥18 years) undergoing OHT between 2000 and 2010. Average institutional volume was calculated during the study period and modeled as a categoric and as a continuous variable. Postoperative complications included rejection, dialysis dependence, infection, stroke, reoperation, and a composite event. Kaplan-Meier estimates and Cox regression modeling were performed for each complication to categorize the unadjusted and adjusted influence of institutional volume on survival.The analysis included 19,849 OHT recipients who were stratified into low-volume (≤14.5 per year), intermediate-volume (14.5-26.5 per year), and high-volume (26.5 per year) tertiles. The overall incidences of postoperative complications were 10.2% for rejection, 7.8% for dialysis dependence, 12.0% for reoperation, 24.1% for infection, and 2.3% for stroke. Recipients in low-volume institutions experienced more complications after OHT than high-volume institutions (43.4% vs 36.2%; p0.001). Survival after the composite complication outcome was significantly worse at 90 days, 1 year, and 5 years in the low-volume cohort. After risk adjustment, low institutional volume (when modeled as a continuous and as a categoric variable) was also independently predictive of mortality at each time point. As expected, survival at 5 years in patients without a postoperative complication (81%; 95 confidence interval [CI], 80.0%-82.8%) was statistically greater (p0.001) than those with 1 (72.8%; 95% CI, 69.9%-75.5%), 2 (59.8%; 95% CI, 54.4%-64.8%), or 3 (39.9%; 95% CI, 31.6%-48.2%) complications.Postoperative complications after OHT have a greater incidence and effect on short-term and long-term survival at low-volume institutions. Accordingly, best practice guidelines established at high-volume institutions could better equip lower-volume hospitals to manage these events in hopes of optimizing transplant outcomes.

Background Although the exact cause of dysphagia after cardiac operations is unknown, timely diagnosis is critical to avoid a devastating aspiration event. Accordingly, we sought to generate the risk of dysphagia in cardiac surgery (RODICS) score to identify patients at risk for its development after heart surgery. Methods All adult heart surgery patients at our institution between January 2011 and March 2012 were analyzed. A videofluoroscopic swallow study stratified patients into two groups based on the presence or absence of dysphagia. Covariates ( p Results During the study period, 115 of 1,314 patients (8.8%) undergoing heart surgery were diagnosed with clinically significant dysphagia. The 38-point RODICS score comprises seven patient-specific characteristics and perioperative factors. The low risk (less than 4), intermediate risk (5 to 9), and high risk (more than 9) cohorts had postoperative dysphagia rates of 3.0%, 6.8%, and 21.6%, respectively ( p p = 0.01) and high-risk cohort (odds ratio 8.9, 95% confidence interval: 5.22 to 15.32, p Conclusions The incidence and impact of dysphagia after open cardiac operations is significant. This novel scoring system could lead to prompt identification of patients at high risk for postoperative dysphagia and potentially minimize the complications of aspiration.

Objective One goal of the Patient Protection and Affordable Care Act is to reduce hospital readmissions, with financial penalties applied for excessive rates of unplanned readmissions within 30 days among Medicare beneficiaries. Recent data indicate that as many as 24% of Medicare patients require readmission after vascular surgery, although the rate of readmission after limited digital amputations has not been specifically examined. The present study was therefore undertaken to define the rate of unplanned readmission among patients after digital amputations and to identify the factors associated with these readmissions to allow the clinician to implement strategies to reduce readmission rates in the future. Methods The electronic medical and billing records of all patients undergoing minor amputations (defined as toe or transmetatarsal amputations using International Classification of Diseases, Ninth Revision, codes) from January 2000 through July 2012 were retrospectively reviewed. Data were collected for procedure- and hospital-related variables, level of amputation, length of stay, time to readmission, and level of reamputation. Patient demographics included hypertension, diabetes, hyperlipidemia, smoking history, and history of myocardial infarction, congestive heart failure, peripheral arterial disease, chronic obstructive pulmonary disease, and cerebrovascular accident. Results Minor amputations were performed in 717 patients (62.2% male), including toe amputations in 565 (72.8%) and transmetatarsal amputations in 152 (19.5%). Readmission occurred in 100 patients (13.9%), including 28 (3.9%) within 30 days, 28 (3.9%) between 30 and 60 days, and 44 (6.1%) >60 days after the index amputation. Multivariable analysis revealed that elective admission ( P P P = .001) were associated with readmission. The reasons for readmission were infection (49%), ischemia (29%), nonhealing wound (19%), and indeterminate (4%). Reamputation occurred in 95 (95%) of the readmitted patients, including limb amputation in 64 (64%) of the patients (below knee in 58, through knee in 2, and above knee in 4). Conclusions Readmission after minor amputation was associated with limb amputation in the majority of cases. This study identified a number of nonmodifiable patient factors that are associated with an increased risk of readmission. Whereas efforts to reduce unplanned hospital readmissions are laudable, payers and regulators should consider these observations in defining unacceptable rates of readmission. Further, although beyond the scope of this study, it is not unreasonable to assume that pressure to reduce readmission rates in the population of patients with extensive comorbidity may induce practitioners to undertake amputation at a higher level initially to minimize the risk of readmission for reamputation and associated financial penalties and thus deprive the patient the chance for limb salvage.

This study evaluated the effect of simultaneous heart-kidney transplantation (SHK) on survival stratified by preoperative renal function.Patients undergoing SHK or heart transplant alone (HTA) between 1992 and 2012 were identified in the United Network for Organ Sharing database. Patients were primarily stratified by the need for dialysis before transplantation. Nondialysis patients were further stratified by preoperative glomerular filtration rate (GFR) and likelihood of postoperative development of renal failure requiring new-onset dialysis (high risk defined as ≥75th percentile according to a previously derived and validated risk score). The primary outcome was 5-year survival, evaluated by Kaplan-Meier and multivariable logistic regression analyses.Included were 665 (2%) SHK and 38,488 (98%) HTA patients. SHK improved 5-year survival in dialysis-dependent patients (69% vs 54%, p0.001), with no survival difference in patients with a preoperative GFR ≥60 mL/min/1.73 m(2) (84% SHK vs 77% HTA, p = 0.34). In patients with a preoperative GFR of less than 60 mL/min/1.73 m(2), being high risk for postoperative new-onset dialysis discriminated those patients who would benefit from SHK (5-year survival low risk: 82% SHK vs 76% HTA, p = 0.27; 5-year survival high risk: 86% SHK vs 67% HTA, p 0.001). Risk-adjusted analysis confirmed these findings. SHK comprised only 2.6% of heart transplants in patients with a preoperative GFR of less than 60 mL/min/1.73 m(2) who were at high risk for postoperative renal failure.SHK improves long-term survival not only in dialysis-dependent patients but also in patients with reduced preoperative GFR who are at high risk for postoperative new-onset dialysis. Expansion of SHK into this subset warrants further study, especially considering its low current utilization.

Background. Despite the significant morbidity associated with renal failure after lung transplantation (LTx), no predictive models currently exist. Accordingly, the purpose of this study was to develop a preoperative risk score based on recipient-, donor-, and transplant-specific characteristics to predict postoperative acute renal failure in candidates for transplantation. Methods. The United Network of Organ Sharing (UNOS) database was queried for adult patients (‡ 18 years of age) undergoing LTx between 2005 and 2012. The population was randomly divided into derivation (80%) and validation (20%) cohorts. The primary outcome of interest was new-onset renal failure. Variables predictive of acute renal failure (exploratory p value < 0.2) within the derivation cohort were incorporated into a multivariable logistic regression model. Odds ratios were used to assign values to the independent predictors of postoperative renal failure to construct the risk stratification score (RSS). Results. During the study period, 10,963 patients underwent lung transplantation, and the incidence of renal failure was 5.5% (598 patients). Baseline recipient-, donor-, and transplant-related factors were similar between the cohorts. Eighteen covariates were included in the multivariable model, and 10 were assigned values based on their relative odds ratios (ORs). Scores were stratified into 3 groups, with an observed rate of acute renal failure of 3.1%, 5.3%, and 15.6% in the low-, moderate-, and high-risk groups, respectively. The incidence of renal failure was found to be significantly increased in the highest risk group (p < 0.001). Furthermore, the risk model’s predicted rates of renal failure highly correlated with actual rates observed in the population (r [ 0.86). Conclusions. We introduce a novel and simple RSS that is highly predictive of renal failure after LTx.

Background Previous studies have demonstrated an association between pretransplantation renal dysfunction (PRD) and increased mortality after lung transplantation (LT). The purpose of this study was to determine whether PRD impacts survival after LT in patients with cystic fibrosis (CF). Methods We queried the United Network for Organ Sharing (UNOS) database to identify all adult (≥18 years) recipients with CF who underwent isolated LT from May 4, 2005 to December 31, 2014. We separated recipients into those with and those without PRD (glomerular filtration rate [GFR] ≤60 mL/min). We excluded patients who required dialysis before transplantation. Kaplan-Meier analysis was used to assess unadjusted survival differences. Cox proportional hazards modeling was then performed across 26 variables to assess the risk-adjusted impact of PRD on 1-, 3-, and 5-year mortality. Results Isolated LT was performed on 1,830 patients with CF; 17 patients were excluded because of pretransplantation dialysis. Eighty-two of 1,813 patients (4.5%) had PRD (GFR ≤60 mL/min). Kaplan-Meier analysis revealed no survival differences between PRD and non-PRD groups at 1 year (85.3% versus 89.5%; log-rank p = 0.23), 3 years (71.0% versus 72.5%; p = 0.57), or 5 years (63.3% versus 59.8%; p = 0.95). After risk adjustment, PRD was not independently associated with an increased hazard for mortality at 1 year (hazard ratio [HR], 1.38 [95% confidence interval [CI], 0.74–2.58]; p = 0.31), 3 years (HR, 1.44 [95% CI, 0.92–2.24]; p = 0.11), or 5 years (HR, 1.30 [95% CI, 0.86–1.94]; p = 0.29). Conclusions Although PRD has historically served as a relative contraindication to LT, our study is the first to suggest that among CF recipients, PRD was not associated with increased hazard for mortality out to 5 years after LT.

Renal cell carcinoma can involve the inferior vena cava and extend into the right atrium. Cure is rarely achieved in patients with concomitant metastases, but cytoreductive nephrectomy and eradication of the entire tumor thrombus can extend survival and prevent symptoms of venous congestion; however, the invasive nature of the tumor thrombus can make resection with negative margins difficult. We present a patient with aggressive renal cell carcinoma that demanded an iliac vein-to-right atrium bypass after inferior vena cava ligation during a previous attempt at curative resection with nephrectomy and caval thrombectomy.