Serum glycomic profile as a predictive biomarker of recurrence in patients with differentiated thyroid cancer.

PURPOSE: Thyroid cancer recurrence following curative thyroidectomy is associated with increased morbidity and mortality, but current surveillance strategies are inadequate for early detection. Prior studies indicate that tissue glycosylation is altered in thyroid cancer, but the utility of serum glycosylation in thyroid cancer surveillance remains unexplored. We therefore assessed the potential utility of altered serum glycomic profile as a tumor-specific target for disease surveillance in recurrent thyroid cancer. EXPERIMENTAL DESIGN: We employed banked serum samples from patients with recurrent thyroid cancer post thyroidectomy and healthy controls. N-glycans were enzymatically released from serum glycoproteins, labeled via permethylation, and analyzed by MALDI-TOF mass spectrometry. Global level and specific subtypes of glycan structures were compared between patients and controls. RESULTS: We evaluated 28 independent samples from 13 patients with cancer recurrence and 15 healthy controls. Global features of glycosylation, including N-glycan class and terminal glycan modifications were similar between groups, but three of 35 individual glycans showed significant differences. The three glycans were biosynthetically related biantennary core fucosylated N-glycans that only varied by the degree of galactosylation (G0F, G1F, and G2F; G: galactose, F: fucose). The ratio of G0F:G1F that captures reduced galactosylation was observed in patients samples but not in healthy controls (p = 0.004) and predicted thyroid cancer recurrence (AUC = 0.82, CI 95% = 0.64-0.99). CONCLUSIONS: Altered N-glycomic profile was associated with thyroid cancer recurrence. This serum-based biomarker would be useful as an effective surveillance tool to improve the care and prognosis of thyroid cancer after prospective validation.

Structural analysis of carbohydrate binding by the macrophage mannose receptor CD206.

The human mannose receptor expressed on macrophages and hepatic endothelial cells scavenges released lysosomal enzymes, glycopeptide fragments of collagen, and pathogenic microorganisms and thus reduces damage following tissue injury. The receptor binds mannose, fucose, or N-acetylglucosamine (GlcNAc) residues on these targets. C-type carbohydrate-recognition domain 4 (CRD4) of the receptor contains the site for Ca2+-dependent interaction with sugars. To investigate the details of CRD4 binding, glycan array screening was used to identify oligosaccharide ligands. The strongest signals were for glycans that contain either Manα1-2Man constituents or fucose in various linkages. The mechanisms of binding to monosaccharides and oligosaccharide substructures present in many of these ligands were examined in multiple crystal structures of CRD4. Binding of mannose residues to CRD4 results primarily from interaction of the equatorial 3- and 4-OH groups with a conserved principal Ca2+ common to almost all sugar-binding C-type CRDs. In the Manα1-2Man complex, supplementary interactions with the reducing mannose residue explain the enhanced affinity for this disaccharide. Bound GlcNAc also interacts with the principal Ca2+ through equatorial 3- and 4-OH groups, whereas fucose residues can bind in several orientations, through either the 2- and 3-OH groups or the 3- and 4-OH groups. Secondary contacts with additional sugars in fucose-containing oligosaccharides, such as the Lewis-a trisaccharide, provide enhanced affinity for these glycans. These results explain many of the biologically important interactions of the mannose receptor with both mammalian glycoproteins and microbes such as yeast and suggest additional classes of ligands that have not been previously identified.

Timing of Recognition for Perioperative Strokes Following Cardiac Surgery.

INTRODUCTION: More than half of reported perioperative strokes following cardiac surgery are identified beyond postoperative day one. The objective of our study was to determine preoperative and intraoperative factors that are associated with stroke following cardiac surgery and to identify factors that may contribute delayed recognition of perioperative stroke. METHODS: Patients undergoing coronary artery bypass surgery or isolated valve surgery from January 2, 2015 to April 28, 2017 at an academic health system were identified from the Society of Thoracic Surgeons Registry. We determined preoperative and intraoperative factors associated with perioperative stroke. Two neurologists performed retrospective chart reviews on perioperative stroke patients to determine the last seen well time and the stroke cause. RESULTS: During the study period, 2795 patients underwent coronary artery bypass surgery or isolated valve surgery (mean age 64 ± 11 years, 71% male, 72% Caucasian, 9% history of stroke), of which 43 (1.5%) had a perioperative stroke; 31 (72%) patients had an embolic mechanism of stroke based on neuroimaging. In multivariable analysis, perioperative strokes were independently associated with increasing age (OR 1.04, 95% 1.01-1.07), history of stroke (OR 2.73, 95% CI 1.47-5.06), and history of thoracic aorta disease (OR 3.36, 95% CI 1.16-9.71). Strokes were identified after postoperative day one in 32 (74%) patients of which 26 (81%) had a preoperative last seen well time. CONCLUSION: Given the high frequency of preoperative last seen well time in perioperative stroke patients who are identified after postoperative day one, delayed stroke recognition may contribute to the bimodal distribution in timing of perioperative stroke. Frequent neurological monitoring within 24 hours after CABG or isolated valve surgery should be considered for all patients undergoing cardiac surgery, particularly elderly patients and those with a history of stroke or thoracic aorta disease, to improve early stroke recognition.

Structural Characterization of Cuta- and Tusavirus: Insight into Protoparvoviruses Capsid Morphology.

Several members of the Protoparvovirus genus, capable of infecting humans, have been recently discovered, including cutavirus (CuV) and tusavirus (TuV). To begin the characterization of these viruses, we have used cryo-electron microscopy and image reconstruction to determine their capsid structures to ~2.9 Å resolution, and glycan array and cell-based assays to identify glycans utilized for cellular entry. Structural comparisons show that the CuV and TuV capsids share common features with other parvoviruses, including an eight-stranded anti-parallel ß-barrel, depressions at the icosahedral 2-fold and surrounding the 5-fold axes, and a channel at the 5-fold axes. However, the viruses exhibit significant topological differences in their viral protein surface loops. These result in three separated 3-fold protrusions, similar to the bufaviruses also infecting humans, suggesting a host-driven structure evolution. The surface loops contain residues involved in receptor binding, cellular trafficking, and antigenic reactivity in other parvoviruses. In addition, terminal sialic acid was identified as the glycan potentially utilized by both CuV and TuV for cellular entry, with TuV showing additional recognition of poly-sialic acid and sialylated Lewis X (sLeXLeXLeX) motifs reported to be upregulated in neurotropic and cancer cells, respectively. These structures provide a platform for annotating the cellular interactions of these human pathogens.

Amplification and Preparation of Cellular O-Glycomes for Functional Glycomics.

Mucin-type O-glycans play key roles in many cellular processes, and they are often altered in human diseases. A major challenge in studying the role of O-glycans through functional O-glycomics is the absence of a complete repertoire of the glycans that comprise the human O-glycome. Here we describe a cellular O-glycome preparation strategy, Preparative Cellular O-Glycome Reporter/Amplification (pCORA), that introduces 4-N3-Bn-GalNAc(Ac)3 as a novel precursor in large-scale cell cultures to generate usable amounts of O-glycans as a potential O-glycome factory. Cultured human non-small cell lung cancer (NSCLC) A549 cells take up the precursor, which is extended by cellular glycosyltransferases to produce 4-N3-Bn-α-O-glycans that are secreted into the culture medium. The O-glycan derivatives can be clicked with a fluorescent bifunctional tag that allows multidimensional HPLC purification and production of a tagged glycan library, representing the O-glycome of the corresponding cells. We obtained ∼5% conversion of precursor to O-glycans and purified a tagged O-glycan library of over 100 O-glycan derivatives, many of which were present in >100 nmol amounts and were sequenced by sequential MS fragmentation (MSn). These O-glycans were successfully printed onto epoxy glass slides as an O-glycome shotgun microarray. We used this novel array to explore binding activity of serum IgM in healthy persons and NSCLC patients at different cancer stages. This novel strategy provides access to complex O-glycans in significant quantities and may offer a new route to discovery of potential diagnostic disease biomarkers.

Heparin-Induced Thrombocytopenia in Patients Undergoing Valvular and Aortic Surgery: A Modern Assessment of Risk.

OBJECTIVE: The incidence and outcomes of patients with heparin-induced thrombocytopenia (HIT) are well defined for general cardiac surgical populations. The purpose of this study was to define the outcomes of patients with HIT in a population excluding patients who underwent coronary artery bypass grafting (CABG). METHODS: The local Society of Thoracic Surgeons cardiac surgical database was queried between January 2008 and May 2017 for patients who underwent either open valvular surgery or aortic surgery. Patients who underwent either isolated or combined CABG procedures were excluded. Cohorts were formed based on the presence or absence of postoperative HIT. Logistic regression models were built to determine the association between postoperative HIT and outcomes, adjusted for both preoperative and intraoperative variables. RESULTS: Of the total cohort (8,107 patients), 176 patients (2.2%) developed HIT after surgery. HIT patients experienced an increased incidence of morbidities postoperatively, including reoperation for bleeding, reoperation for cardiac and noncardiac etiologies, postoperative stroke, perioperative myocardial infarction, postoperative sternal infection, postoperative arrhythmia, new-onset renal failure, and dialysis (all with P < 0.01). The unadjusted 30-day mortality was 14.8% in HIT patients vs 4.9% in those without HIT (P < 0.01). After risk adjustment, reoperation for noncardiac events, renal failure, new dialysis, postoperative stroke, arrhythmia, and sternal wound infection remained significantly elevated in patients who developed postoperative HIT. CONCLUSIONS: Patients who developed HIT after non-CABG cardiac surgery experienced increased postoperative rates of morbidity and mortality. Early diagnosis and treatment remained mainstays of therapy. Early identification of patients at highest risk should prompt careful risk stratification when possible.

Self-reported sleep disturbance in Crohn's disease is not confirmed by objective sleep measures.

Sleep disturbance and fatigue are commonly reported among patients with Crohn's disease (CD). In this prospective study, we aimed to define sleep quality in CD patients at various disease activity states and compare to healthy controls using objective and subjective measures. A prospective observational cohort study of CD patients seen at a tertiary academic inflammatory bowel diseases (IBD) clinic was compared to healthy volunteers. CD activity was assessed using the Harvey-Bradshaw Index (HBI). Sleep quality was assessed using the Pittsburgh Sleep Quality Index (PSQI) and Epworth Sleepiness Scale (ESS) and objectively over 1-week using actigraphy (motion-based) and morning urinary melatonin metabolite. 121 subjects (CD patients N = 61; controls N = 60) completed the study. 34 had active CD (HBI > 4). Sleep disturbance was more frequently reported by CD subjects than controls (PSQI: 57% vs. 35%, p = 0.02) and in patients with active CD versus in remission state (PSQI 75.8% vs. 33.3%, p < 0.01; ESS: 45.5% vs. 19%, p = 0.03). Sleep parameters as measured by actigraphy and urine melatonin metabolite did not vary by group. Crohn's patients report significantly more disturbed sleep than controls. However, poor sleep was not confirmed by objective measures of sleep quality. Excessive daytime sleepiness in CD patients may be driven by factors beyond objectively measured poor sleep.

Valve Sparing Root Replacement Provides Similar Midterm Outcomes in Bicuspid and Trileaflet Valves.

BACKGROUND: Valve-sparing aortic root replacement (VSRR) is an established treatment for aortic root pathology for trileaflet valves. The safety and durability of VSRR in bicuspid aortopathy is unclear. In this study, outcomes of performing VSRR in the setting of bicuspid and trileaflet valves were compared. METHODS: An institutional database identified 294 patients who underwent VSRR from 2005 to 2017. Of these, 225 had trileaflet valves and 69 had bicuspid valves. Patients were followed prospectively and had annual postoperative echocardiograms. Propensity-matched comparisons were made between trileaflet and bicuspid valve patients. RESULTS: The average patient age for trileaflet valves was 46.0 ± 13.5 versus 42.7 ± 12.2 years for bicuspid patients (p = 0.07). There was a higher presence of preoperative >2+ aortic insufficiency (AI) present in bicuspid patients (63.8%) compared with trileaflet patients (31.1%) (p < 0.01). Mean follow-up was 39 months and was 98% complete. At 5 years, the cumulative incidence of >2+ AI and aortic valve replacement (AVR) was 2.0% and 4.3% in trileaflet patients and 7.7% (p = 0.75) and 7.7% (p = 0.81) in bicuspid patients. Preoperative >2+ AI was not predictive of >2+ postoperative AI (p = 0.62) nor AVR (p = 0.49). Five-year survival was no different between groups (trileaflet: 98%, bicuspid: 84%, p = 0.24). CONCLUSIONS: VSRR can be safely and effectively performed in patients with trileaflet and bicuspid valves. Operative outcomes and valve function were equivalent in bicuspid and trileaflet patients in midterm follow-up. Performance of VSRR is a viable term option in the setting bicuspid aortic valve aortopathy.

Valve-Sparing Root Replacement Provides Excellent Midterm Outcomes for Bicuspid Valve Aortopathy.

BACKGROUND: Standard therapy for aortic root dilation in the setting of bicuspid aortic valves remains use of a composite valve conduit. The long-term durability of valve-sparing root replacement (VSRR) in bicuspid aortopathy is presently unclear. In this study, the midterm results of performing VSRR in the setting of a bicuspid valve was analyzed. METHODS: A single institutional database identified 280 patients who underwent VSRR from 2005 to 2016. Outcomes were analyzed in 60 consecutive patients undergoing a VSRR in the setting of a bicuspid aortic valve with aortic insufficiency (AI). Patients were followed prospectively and had annual echocardiograms. RESULTS: The average age in this series was 42 ± 11 years. Eighty percent were men and 33% had New York Heart Association class III to IV symptoms. More than 2+ AI was present in 42% of patients preoperatively. The incidence of operative death, stroke, and renal failure was 0%. Mean follow-up was 39 ± 30 months. At latest follow-up, 62% of patients had zero AI and 87% of patients had <1+ AI. At 5 years, freedom from >2+ AI was 97% and freedom from AVR was 96%. Preoperative AI was not found to be a significant risk factor for postoperative >2+ AI (p = 0.61) or AVR (p = 0.61). CONCLUSIONS: VSRR can be safely and effectively performed in young patients with bicuspid valve anatomy regardless of degree of preoperative AI. Valve function is durable and the incidence of valve-related complications is low. VSRR is an attractive and potentially superior option to conventional root replacement in appropriately selected patients with bicuspid aortopathy.

Durability and safety of David V valve-sparing root replacement in acute type A aortic dissection.

BACKGROUND: Valve-sparing root replacement (VSRR) is an attractive option in type A aortic dissection (TAAD) repair for a young patient with normal cusp anatomy, but conventional root replacement using a composite valved-conduit (ROOT) remains the gold standard in this emergent clinical setting. We examine the long-term safety and durability of the David V VSRR compared with ROOT in TAAD repair. METHODS: From March 2004 to April 2017, 136 patients underwent repair of acute TAAD using either ROOT (n = 77; 56.6%) or VSRR (n = 59; 43.4%). Annual echocardiograms were performed for follow-up in VSRR patients. Univariable regression, Kaplan-Meier, and competing risk analyses were performed. RESULTS: Preoperative characteristics were similar between groups, except that VSRR patients were younger (mean age 43.5 ± 11.4 years VSRR vs 50.4 ± 3.0 years ROOT; P = .001). Both groups had similar rates of preoperative malperfusion or shock (29.3% VSRR vs 37.0% ROOT; P = .35) and ≥3+ aortic insufficiency (63% VSRR vs 76.8% ROOT). Thirty-day mortality in the VSRR group was 2/59 (3.4%) and 11/77 in the ROOT group (14.3%; P < .001). All-cause survival at 9 years was 92% (VSRR) and 59% (ROOT; P = .002). The incidence of aortic reintervention was similar between groups (20%-23% at 5 years; P = .81). At 9 years of follow-up, 5/52 (9.6%) VSRR patients had ≥2+ aortic insufficiency, and 1 patient required valve reintervention. CONCLUSIONS: In highly-selected patients, the David V VSRR provides a safe repair of acute TAAD with concomitant root pathology and valve insufficiency. In our center, the incidence of valve-related reintervention at long-term follow-up is low after emergent repair.

The evidence in a Bentall procedure with Valsalva graft: is this standard of care?

BACKGROUND: Biologic valved-conduits avoids the need for anticoagulation and can exploit the excellent hemodynamic performance of stentless valves. Incorporation of the sinuses of Valsalva into the neoaortic root can improve the function and longevity of stentless valves. We report our experience in performing the Bentall procedure with a self-prefabricated composite valved-conduit and review the published experience with the Valsalva graft. METHODS: From Feb 2005 through Sep 2017, 428 patients underwent aortic root replacement utilizing a composite graft constructed from a 27-29-mm Freestyle MS valve (Medtronic) sutured into a 28-30-mm Gelweave Valsalva prosthesis (Sulzer Vascutek, Renfrewshire, Scotland). Data were retrospectively analyzed. RESULTS: Mean age was 58±13 years, with a male predominance (337, 79%). Additional surgical procedures included a mitral valve repair/replacement in 10 patients (2%), coronary artery bypass graft (CABG) in 114 patients (27%), and aortic arch (hemi or total) replacement in 252 patients (59%). Average cardiopulmonary bypass, cross-clamp, and circulatory arrest times were 210±57, 180±44, and 29±15 min, respectively. Thirty-day mortality was 7% (31 patients). Mean echocardiography follow-up was 27.2±29.0 months (range, 1-138 months). Pressure gradients (mean, peak) across the aortic valve on latest echocardiography were 5.59, 10.57 mmHg respectively. Freedom from >2+ aortic insufficiency (AI) at 6 and 9 years was 96%, and 87% respectively. Freedom from aortic valve replacement (AVR) at 6 and 9 years was 99%, and 95% respectively. To date, 4 (1%) patients required an additional aortic valve intervention secondary to structural valve degeneration. CONCLUSIONS: Use of the Valsalva graft combined with the Freestyle valve for Bentall procedures is associated with favorable results. Clinical outcomes are excellent and in longitudinal follow-up, valve-related complications are minimal.

Bicuspid aortic valve repair in the setting of severe aortic insufficiency.

BACKGROUND: Bicuspid aortic valve (BAV) is a common cardiac anomaly that affects 0.5-2% of adults. Valve sparing root replacement (VSRR) in bicuspid aortopathy is gaining popularity. We discuss the technical aspects of the procedure as well as the mid- to long-term results of performing VSRR in the setting of a bicuspid valve. METHODS: A single institutional database identified 280 patients who underwent VSRR from 2005-2016. Outcomes were analyzed in 60 consecutive patients undergoing a VSRR in the setting of a BAV with aortic regurgitation (AR). Patients were followed prospectively and had annual echocardiograms. RESULTS: The average age in this series was 42±11 years. Moderate or more AR was present in 50% of patients preoperatively. The incidence of operative death, stroke, and renal failure was 0%. Mean follow-up was 39±30 months. At latest follow-up, 62% of patients had zero AR and 87% of patients had <1+ AR. At 9 years, freedom from >2+ AR was 97% and freedom from aortic valve repair (AVR) was 96%. CONCLUSIONS: VSRR can be safely and effectively performed in young patients with bicuspid valve anatomy regardless of degree of pre-operative AR. Valve function is durable and the incidence of valve-related complications is low. VSRR is an attractive and potentially superior option to conventional root replacement in appropriately selected patients with bicuspid aortopathy.

Operative strategies to reduce cerebral embolic events during on- and off-pump coronary artery bypass surgery: A stratified, prospective randomized trial.

OBJECTIVE: To determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). METHODS: Between 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy. Transcranial Doppler ultrasonography (TCD) was performed to identify high-intensity transient signals (HITS) in the middle cerebral arteries during periods of aortic manipulation. Neurocognitive testing was performed at baseline and 30-days postoperatively. The primary endpoint was total number of HITS detected by TCD. Groups were compared using the Mann-Whitney U test. RESULTS: In the off-pump group, the median number of total HITS were higher in the CFD subgroup (30.0; interquartile range [IQR], 22-43) compared with the partial clamp subgroup (7.0; IQR, 0-16; P < .0001). In the CFD subgroup, the median number of total HITS was significantly lower for patients with 1 CFD compared with patients with >1 CFD (12.5 [IQR, 4-19] vs 36.0 [IQR, 25-47]; P = .001). In the on-pump group, the median number of total HITS was 10.0 (IQR, 3-17) in the single-clamp group, compared with 16.0 (IQR, 4-49) in the double-clamp group (P = .10). There were no differences in neurocognitive outcomes across the groups. CONCLUSIONS: For patients with low-grade aortic disease, the use of CFDs was associated with an increased rate of cerebral embolic events compared with partial clamping during off-pump CABG. A single-clamp strategy during on-pump CABG did not significantly reduce embolic events compared with a double-clamp strategy.

Risk Factors for Late Aortic Valve Dysfunction After the David V Valve-Sparing Root Replacement.

BACKGROUND: Valve-sparing root replacement (VSRR) is an established therapy for aortic root pathology. However, late aortic valve dysfunction requiring reoperation remains a primary concern of this procedure. This study examines risk factors for late aortic insufficiency (AI) and aortic stenosis (AS) after David V VSRR. METHODS: A retrospective review from 2005 to 2015 at a US academic center identified 282 patients who underwent VSRR. Cox proportional hazards regression analysis was used to identify risk factors for late AI and AS after VSRR. RESULTS: The mean age was 46.4 years. Sixty-four patients (22.7%) had bicuspid valves, and 41 patients (14.5%) had Marfan syndrome. The incidence of reoperations was 27 (9.6%), and 42 cases (14.9%) presented with acute type A dissection. Operative mortality was 8 (2.8%). Seven-year survival was 90.9%. Seven-year cumulative incidence of reoperation, greater than 2+ AI and greater than moderate AS were 3.1%, 2.2%, and 0.8%, respectively. Multivariable analysis showed aortic root size 55 mm or larger (hazard ratio 3.44, 95% confidence interval: 1.27 to 9.29, p = 0.01) to be a risk factor for late AI whereas bicuspid valve (hazard ratio 16.07, 95% confidence interval: 3.12 to 82.68, p = 0.001) and cusp repair were found to be risk factors (hazard ratio 5.91, 95% confidence interval: 1.17 to 29.86, p = 0.03) for late AS. CONCLUSIONS: Valve-sparing root replacement can be performed with low operative risk and good overall long-term survival even in complex clinical settings. Durable valve function can be expected; however, aortic root size 55 cm or more, bicuspid valve anatomy, and cusp repair represent independent risk factors for late aortic valve dysfunction after these procedures.

Reoperative aortic root replacement: Outcome in a contemporary series.

OBJECTIVES: Reoperative aortic root replacement is a challenging procedure associated with significant mortality and morbidity. The purpose of this study was to investigate the outcomes of reoperative aortic root replacement when performed in a number of complex clinical settings and to identify risk factors for operative mortality and long-term survival. METHODS: From 2006 to 2015, 280 consecutive patients at an academic center underwent reoperative aortic root replacement after a variety of previous aortic or cardiac operations. Logistic regression and extended Cox proportional hazards regression analyses were used to determine risk factors for operative mortality and long-term survival, respectively. RESULTS: The mean age of patients was 52.5 ± 14.1 years. Prior operations included proximal aortic replacement in 113 patients, valve surgery in 162 patients, and coronary artery bypass grafting in 46 patients. Concomitant procedures included arch replacement in 135 patients, coronary artery bypass grafting in 68 patients, and mitral valve repair/replacement in 18 patients. Operative mortality was 14.3%. Five-year survival was 74.0%. Univariable analysis did not find previous root replacement, prior proximal aortic surgery, and concomitant arch replacement to be risk factors for operative mortality. In the multivariable analysis, chronic lung disease, prior myocardial infarction, and concomitant mitral valve surgery were risk factors for operative mortality. Age, peripheral artery disease, emergency, and concomitant mitral valve surgery were risk factors for mortality in the late phase. CONCLUSIONS: Reoperative aortic root replacement represents complex procedures carrying significant morbidity and mortality. Chronic lung disease, prior myocardial infarction, and concomitant mitral valve surgery were risk factors for operative mortality. Age, peripheral artery disease, emergency, and concomitant mitral valve surgery were risk factors for long-term mortality.

Readmission rates after transcatheter aortic valve replacement in high- and extreme-risk patients with severe aortic stenosis.

OBJECTIVE: In high- or extreme-risk patients undergoing transcatheter aortic valve replacement, readmissions have not been adequately studied and are the subject of increased scrutiny by healthcare systems. The objectives of this study were to determine the incidence of 30-day and 1-year cardiac and noncardiac readmissions, identify predictors of readmission, and assess the association between readmission and 1-year mortality. METHODS: A retrospective review was performed on 714 patients who underwent transcatheter aortic valve replacement from September 2007 to January 2015 at Emory University. RESULTS: Patients' median age was 83 years, and 46.6% were female. Early all-cause readmission for the cohort was 10.5%, and late readmission was 18.8%. Anemia was related to both early all-cause (hazard ratio [HR], 0.74) and cardiovascular-related readmission (HR, 0.60). A 23-mm valve implanted was associated with early all-cause readmission (HR, 1.73). Length of hospital stay was related to late all-cause (HR, 1.14) and cardiovascular-related readmission (HR, 1.21). Postoperative permanent stroke had an impact on late cardiovascular-related readmission (HR, 3.60; 95% confidence interval, 1.13-11.49). Multivariable analysis identified anemia as being associated with 30-day all-cause readmission, and anemia and postoperative stroke were associated with 30-day cardiovascular-related readmission. Readmissions seemed to be related to 1-year mortality (HR, 2.04; 95% confidence interval, 1.33-3.12). CONCLUSIONS: We show some baseline comorbidities and procedural complications that are directly associated with early and late readmissions, and anemia and postoperative stroke were associated with an increase in mortality. Moreover, we found that readmission was associated with double the hazard of death within 1 year. Whether treatment of identified risk factors could decrease readmission rates and mortality warrants further investigation.

Pilot Study to Integrate Patient Reported Outcomes After Lung Cancer Operations Into The Society of Thoracic Surgeons Database.

BACKGROUND: A critical gap in The Society of Thoracic Surgeons (STS) Database is the absence of patient-reported outcomes (PRO), which are of increasing importance in outcomes and performance measurement. Our aim was to demonstrate the feasibility of integrating PRO into the STS Database for patients undergoing lung cancer operations. METHODS: The National Institutes of Health Patient Reported Outcome Measurement Information System (PROMIS) includes reliable, precise measures of PRO. We used validated item banks within PROMIS to develop a survey for patients undergoing lung cancer resection. PRO data were prospectively collected electronically on tablet devices and merged with our institutional STS data. Patients were enrolled over 18 months (November 2014 to May 2016). The survey was administered preoperatively and at 1 and 6 months after lung cancer resection. RESULTS: The study included 127 patients. All patients completed the initial postoperative survey, and 108 reached the 6-month follow-up. The most common procedure was video-assisted thoracic lobectomy (55%). At the first postoperative visit, there was a significant increase in pain, fatigue, and sleep impairment and a decrease in physical function. By 6 months, these PRO measures had generally improved toward baseline. CONCLUSIONS: Collecting PRO data from lung cancer surgical patients and integrating the results into an institutional database is feasible. This pilot serves as a model for widespread incorporation of PRO data into the STS Database. Future integration of such data will continue to position the STS National Database as the gold standard for clinical registries. This will be necessary for assessing overall patient responses to different surgical therapies.

Clinical Outcomes of the David V Valve-Sparing Root Replacement Compared With Bioprosthetic Valve-Conduits for Aortic Root Aneurysms.

BACKGROUND: Valve-sparing root replacement (VSRR) is an established therapy for aortic root pathology. Limited insight exists when the results of VSRR are compared with those of conventional root replacement with use of a bioprosthetic composite conduit (BIO). This study compares the operative and midterm results of VSRR and BIO. METHODS: A retrospective review from 2002 to 2015 at a United States academic center identified 282 patients who underwent VSRR and 425 patients who underwent BIO. Propensity-score matching was performed based on 20 preoperative characteristics, and 123 matched pairs were identified. RESULTS: The mean age (VSRR 53.5 ± 11.1, BIO 53.0 ± 13.0; p = 0.74) and left ventricular ejection fraction (VSRR 54.5 ± 9.2%, BIO 54.4 ± 9.4%; p = 0.99) were equivalent in both groups. The incidence of bicuspid valves (VSRR 26.0%, BIO 27.6%; p = 0.77), Marfan syndrome (VSRR 6.5%, BIO 4.9%; p = 0.58), type A dissection (VSRR 13.0%, BIO 13.0%; p = 0.99), reoperation (VSRR 15.4%, BIO 20.3%; p = 0.32) and arch replacement (VSRR 60.2%, BIO 63.4%; p = 0.60) were similar between the groups. Operative mortality was 5.7% in VSRR and 0.8% in BIO (p = 0.07). There were no significant differences in postoperative renal failure (VSRR 0.8%, BIO 0.0%; p = 0.99) or stroke (VSRR 3.3%, BIO 0.8%; p = 0.37) between the groups. The 7-year survival (VSSR 82.4%, BIO 83.0%; p = 0.53), 7-year freedom from reoperation (VSRR 97.4%, BIO 95.8%; p = 0.48), and 7-year freedom from greater than moderate aortic insufficiency (AI) (VSRR 98.1%, BIO 100.0%; p = 0.47) were similar between groups. CONCLUSIONS: VSRR and BIO result in equivalent operative mortality and morbidity with similar midterm survival and valve durability. VSRR is an effective alternative to BIO for aortic root pathologic conditions; however, careful patient selection is paramount.

Severity of Preoperative Aortic Regurgitation Does Not Impact Valve Durability of Aortic Valve Repair Following the David V Valve Sparing Aortic Root Replacement.

BACKGROUND: The David V valve-sparing aortic root replacement (VSRR) is an established and durable method of root reconstruction for varying pathologies. However, the impact of the severity of preoperative aortic regurgitation (AR) on long-term durability remains unclear. The purpose of this research was to investigate the impact of the degree of preoperative AR on midterm durability following VSRR. METHODS: A retrospective review of the adult cardiac surgical database at a single academic center was undertaken from 2005 to 2015 for 223 adult patients who underwent VSRR. Patients were followed annually with echocardiograms, and a prospectively maintained database kept track of patient data. Follow-up was 97.7% complete, and the median echocardiographic follow-up was 25.5 months (range, 1 to 123 months). Patients with preoperative AR less than or equal to 2 were compared with patients with AR greater than 2 to determine the impact of preoperative AR upon valve repair durability. RESULTS: There were 223 patients who underwent VSRR during the study period, including 114 (51.1%) who required concomitant cusp repair. The operative mortality was 5 (2.2%). Ninety-seven patients (43.5%) had preoperative AR greater than 2. A total of 213 patients (95.5%) were available for long-term follow-up; of these patients, 7 (3.3%) had AR greater than 2. Fifty-two patients had a bicuspid aortic valve (22 AR ≤2 and 30 AR >2; p = 0.02). Patients with preoperative AR greater than 2 experienced greater reverse left ventricular remodeling and increases in left ventricular ejection fraction than did patients with preoperative AR less than or equal to 2 (p < 0.01). The midterm freedom from AR greater than 2 was similar for both preoperative AR groups (p = 0.57). The 8-year freedom from AR greater than 2 was 89.1% (95% confidence interval, 55.3% to 97.8%) for patients with preoperative AR less than or equal to 2 and 92.7% (95% confidence interval, 78.8% to 97.6%) for preoperative AR greater than 2. Five patients (2.4%) required aortic valve replacement during the follow-up period (3 preoperative AR ≤2, 2 preoperative AR >2). CONCLUSIONS: VSRR remains an effective and durable treatment for severe AR and preserved leaflet architecture. The severity of preoperative AR does not appear to impact midterm freedom from moderate to severe AR. VSRR results in significant left ventricular remodeling in patients with preoperative AR greater than 2.

The David V Valve-Sparing Root Replacement Provides Improved Survival Compared With Mechanical Valve-conduits in the Treatment of Young Patients With Aortic Root Pathology.

BACKGROUND: Valve-sparing root replacement (VSRR) is an attractive therapy for aortic root aneurysms; however, there is a paucity of data comparing VSRR with conventional root replacement using a mechanical valve-conduit (MECH). This study evaluates and compares outcomes of VSRR and MECH. METHODS: A retrospective review from 2002 to 2015 at a US academic center identified 444 patients who underwent VSRR (282 patients) or MECH (162 patients). Propensity score matching was performed, based on 22 preoperative and intraoperative characteristics, and 87 matched pairs were identified. RESULTS: There was no difference in mean age between the groups (VSRR 45.0 years, MECH 44.2 years, p = 0.59). The incidence of Marfan syndrome (VSRR 10.3%, MECH 12.6%, p = 0.63), type A acute aortic dissection (VSRR 25.3%, MECH 27.6%, p = 0.73), reoperation (VSRR 23.0%, MECH 21.8%, p = 0.86), and arch replacement (VSRR 54.0%, MECH 52.9%, p = 0.88) were similar in both groups. Ejection fraction was similar (VSRR 52.8% ± 10.9%, MECH 52.4% ± 11.7%, p = 0.83). Operative mortality was 2.3% with VSRR and 8.0% with MECH (p = 0.10). There were no significant differences in renal failure requiring dialysis (VSRR 1.1%, MECH 4.6%, p = 0.24), permanent neurologic dysfunction (VSRR 2.3%, MECH 6.9%, p = 0.16), and pacemaker implantation (VSRR 1.1%, MECH 1.1%, p = 0.99) between the groups. Survival at 7 years was significantly improved in patients who underwent VSSR (VSRR 85.5%, MECH 73.6%, p = 0.03). CONCLUSIONS: In comparison with patients undergoing MECH, there is improved midterm survival among patients undergoing VSRR, with similar operative mortality and morbidity. For appropriately selected patients, VSRR provides an attractive and potentially superior alternative to MECH.