Search

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 purpose of this study was to describe levels of adherence to guideline-based medical management in patients with aortic aneurysms, using an analogous population with coronary artery disease as a comparator. Adherence among those with aortic aneurysms has never been studied.Adult patients with an aortic aneurysm or coronary artery disease diagnosed between 2004 and 2018 in the Optum Clinformatics deidentified Datamart were queried. Aneurysms were subclassified as thoracic, abdominal, or both. Receipt of an antihypertensive or antihyperlipidemic was determined through pharmacy claims. Adherence was determined as receipt of the indicated pharmacologic(s) after a diagnosis of aneurysm or coronary artery disease. Adherence was compared between those with aneurysms and coronary disease using univariable logistic regression.After exclusions, 194,144 patients with an aortic aneurysm and 3,946,782 with coronary artery disease were identified. Overall adherence was low (45.0%) and differed significantly by aneurysm subtype: highest in isolated thoracic (45.9%) and lowest in isolated abdominal aneurysms (42.6%). Adherence levels declined significantly after 1 year by about 15% in each aneurysm subtype. All subtypes of aneurysm had a significantly lower odds of adherence compared to those with coronary disease with odds ranging from 0.61 in those with isolated abdominal aneurysms to 0.80 with isolated thoracic aneurysms.Adherence among those with aortic aneurysms is very low, differs by subtype, and declines with time. Levels of adherence in those with aortic aneurysms is significantly lower compared to those with coronary artery disease. This should prove a reasonable target for implementation initiatives.

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.

The use left ventricular assist devices (LVAD) as a bridge-to-transplant (BTT) has become a common modality to treat end-stage heart failure. We sought to examine the impact of BTT on long-term survival and quality of life after heart transplant. The population was all adult patients undergoing isolated heart transplantation in the United States between 2007 and 2017. Inclusion criteria covered BTT patients with a LVAD (only Heartmate II [HMII] or HeartWare Ventricular Assist System [HVAD]) and compared these with patients undergoing de novo heart transplantation. Our primary end-point was survival at 1, 2, and 5 years. Secondary end-points were functional status, return to work, and rates of hospital readmission and graft rejection. Unconditional and conditional survival was estimated with the Kaplan-Meier method. The independent influence of BTT on risk-adjusted mortality was determined using Cox proportional hazards models. In this period, 5,584 patients were bridged with an LVAD and 12,295 underwent de novo transplantation. Unconditional survival was 2% higher in de novo patients at 1, 2, and 5 years. After risk adjustment, BTT was associated with increased mortality at each time point. Unadjusted 5 year survival, conditional on 90 day survival, was similar between groups (82.6% vs. 83.4%; p = 0.15). Functional status, return to work, and unadjusted rates of hospital readmission and graft rejection were similar at 1, 2, 5 years. Bridge-to-transplant with LVADs provides excellent survival and similar quality of life to that of patients undergoing de novo heart transplantation. Bridge-to-transplant patients experience a slightly higher mortality rate within 90 days of transplantation.

Background: Given the shortage of donor organs in pediatric heart transplantation (HTx), pretransplant risk stratification may assist in organ allocation and recipient optimization. We sought to construct a scoring system to preoperatively stratify a patient’s risk of one-year mortality after HTx. Methods: The United Network for Organ Sharing database was queried for pediatric (Results: A total of 5,700 patients underwent HTx; one-year mortality was 10.7%. There was a similar distribution of variables between derivation (n = 4,560) and validation (n = 1,140) cohorts. Of the 12 covariates included in the final model, nine were allotted point values. The low-risk (score 0-9), intermediate-risk (10-20), and high-risk (>20) groups had a 5.18%, 10%, and 28% risk of one-year mortality ( P < .001), respectively. Both intermediate-risk (OR = 2.46, 95% confidence interval [95% CI]: 1.93-3.15; P < .001) and high-risk (OR = 9.24, 95% CI: 6.92-12.35; P < .001) scores were associated with an increased risk of one-year mortality when compared to the low-risk group. Conclusions: The Children’s Heart Assessment Tool for Transplantation score represents a pediatric-specific, recipient-based system to predict one-year mortality after HTx. Its use could assist providers in identification of patients at highest risk of poor outcomes and may aid in pretransplant optimization of these children.

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.

We assessed the impact of donor multiorgan procurement on survival following orthotopic heart transplantation (OHT). From the UNOS STAR database, we included all adult (≥18 Y) heart transplants (OHT) performed since 2000 and used donor IDs to determine how many other organs were procured from the same donor as the recipient's heart allograft (regardless of recipient). The Kaplan-Meier survival functions and risk-adjusted Cox proportional hazards regression models were computed to assess the association of multiorgan procurement with post-heart transplantation mortality. We included 40 336 OHT patients. Including the heart, the median number of donor organs procured was 3 (IQR, 3-4). Heart donors underwent liver procurement in 89.7%; kidney(s) in 98.1% (single 95%, bilateral 5%); lung(s) in 38.0% (single 28%, bilateral 72%); pancreas in 10.4%; and intestine in 1.6%. Following risk adjustment across 16 recipient- and donor-specific variables, an increasing number of organs procured were independently associated with reduced post-OHT mortality (HR 0.98, 95% CI 0.96-0.99, P = .025). Though no significant associations were found examining specific organ types, double lung procurement trended toward a protective effect (HR 0.96, 0.92-1.01, P = .086), with counts of non-lung organs procured still bordering on significance (HR 0.97, 95% CI 0.95-1.00, P = .067). These results likely reflect improved multiorgan donor quality.

Objectives We sought to develop strategies for management of the aortic arch in patients with Loeys–Dietz syndrome (LDS) through a review of our clinical experience with these patients and a comparison with our experience in patients with Marfan syndrome (MFS). Methods We reviewed hospital and follow-up records of 79 patients with LDS and compared them with 256 patients with MFS who served as reference controls. Results In the LDS group, 16% of patients presented initially with acute aortic dissection (AAD) (67% type A, 33% type B) or developed AAD during follow-up, compared with 10% of patients with MFS (95% type A, 5% type B). There was no difference between patients with LDS or MFS in need for subsequent arch interventions after aortic root surgery (46% vs 50%, P = 1.0). Among the patients who never had AAD, the need for arch repair at initial root surgery was greater in patients with LDS (5% vs 0.4%, P = .04), as was the need for any subsequent aortic surgery (12% vs 1.3%, P = .0004). Late mortality in patients with LDS after arch repair was greater than in those patients who had no arch intervention (33% vs 6%, P = .007). Conclusions In the absence of dissection, patients with LDS have a greater rate of arch intervention after root surgery than patients with MFS. After a dissection, arch reintervention rates are similar in the 2 groups. Arch intervention portends greater late mortality in LDS.

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.

Background Loeys–Dietz syndrome (LDS) is characterized by a triad of aortic aneurysm, vessel tortuosity, and hypertelorism. LDS patients often harbor additional aneurysms and dissections throughout their vasculature. The optimal management of these additional lesions is poorly understood. Accordingly, we sought to analyze our experience with the peripheral arterial manifestations of LDS. Methods Adult and pediatric LDS patients who sought treatment at a single institution from 2005 to 2015 were retrospectively reviewed. Patients were included if radiographic or clinically documented evidence existed of peripheral artery aneurysm or dissection. Standard univariate analyses were performed. Results Eighteen LDS patients (aged 1.3–59.3 years, mean age 27.8 years at diagnosis) with aortic (not including root, ascending, or arch) vascular abnormalities were identified. Average follow-up was 5.2 ± 3.8 years. Fourteen (77.8%) patients had peripheral aneurysms, occurring most frequently in the carotid (35.7%), subclavian (35.7%), and visceral (28.6%) segments. Most patients had multiple peripheral segments involved (average 2, range 1–6). Nine (64%) patients with peripheral involvement underwent repair, for a total of 17 operations (average 1.89 operations per patient, range 1–4). Endovascular techniques were used in 4 operations (23.5%), without technical failures. Among patients requiring surgical repair, a history of abdominal aortic repairs was present in 77.8%, yielding a total of 36 vascular repairs (average 4, range 2–7). Perioperative morbidity was 11.8%, with no reported mortalities. Prior aortic dissection was not associated with peripheral surgical repairs (P = 0.58). Conclusions LDS is an aggressive vasculopathy which commonly affects the peripheral vasculature. Our data suggest that open and endovascular procedures may be safe and effective in the LDS periphery and multiple operations are common. As prior aortic dissection did not predict peripheral arterial involvement in LDS, vigilant peripheral arterial surveillance of LDS is warranted regardless of aortic disease state and may be key to early identification and our treatment success.

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.

The goal in the treatment of acute type A aortic dissection (ATAAD) is to resect the primary intimal tear while minimizing associated complications of the disease. This goal can be accomplished by different surgical techniques and operative strategies. The extent of proximal and distal aortic reconstruction and the use of cerebral perfusion adjuncts are highly variable between institutions and within institutions themselves. As operative outcomes for ATAAD have improved considerably over the past decade, the focus has shifted towards extensive aortic reconstruction to minimize aortic reinterventions. However, there remains a distinct difference in how patients with ATAAD are managed in North America when compared with those in East Asia.

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.