Mid-term Waitlist and Posttransplant Outcomes With Hepatitis C-positive Donor Hearts.

BACKGROUND: This study evaluates the clinical trends and impact of hepatitis C virus-positive (HCV+) donors on waitlist and posttransplant outcomes after heart transplantation. METHODS: The United Network for Organ Sharing registry was queried to identify adult waitlisted and transplanted patients from January 1, 2015, to December 31, 2022. In the waitlist analysis, the candidates were stratified into 2 cohorts based on whether they were willing to accept HCV+ donor offers. Waitlist outcomes included 1-y cumulative incidences of transplantation and death/delisting. In the posttransplant analysis, the recipients were stratified into 2 cohorts with and without HCV nucleic acid test (NAT)-positive donors. Outcomes included 1- and 4-y posttransplant survival. Propensity score-matching was performed. Risk adjustment was performed using multivariable Cox regression. RESULTS: During the study period, the number of centers using HCV NAT+ donors increased from 1 to 65 centers, along with the number of transplants. In the waitlist analysis, 26 648 waitlisted candidates were analyzed, and 4535 candidates (17%) were approved to accept HCV+ donors. Approval to accept HCV+ donors was associated with a higher likelihood of transplantation and a lower likelihood of death/delisting within 1 y of waitlisting. In the posttransplant analysis, 21 131 recipients were analyzed, and 997 recipients (4.7%) received HCV NAT+ hearts. The 1- and 4-y posttransplant survival were comparable between the recipients of HCV NAT+ and NAT- donors. Furthermore, the similar 1- and 4-y posttransplant survival persisted in the propensity score-matched comparison and multivariable Cox regression analysis. CONCLUSIONS: Utilization of HCV+ donors is rising. Heart transplants using HCV+ donors are associated with improved waitlist and comparable posttransplant outcomes.

The Natural History of Mitral Regurgitation after Transcatheter Aortic Valve Implantation.

BACKGROUND: To determine the impact of mitral regurgitation (MR) on outcomes after transcatheter aortic valve implantation (TAVI). METHODS: This was an observational study of TAVIs for aortic stenosis (AS) from 11/2012-12/2021. 25% of patients were excluded because post-TAVI echocardiograms were unavailable. Excluded patients had a higher STS-PROM than included patients (5.6% vs. 4.9%). Patients were dichotomized according to the severity of pre-TAVI MR: < moderate vs. ≥ moderate. RESULTS: A total of 2250 patients underwent TAVI, of which 329 (14.6%) had MR ≥ moderate before TAVI. Baseline MR ≥ moderate was associated with reduced survival [46.2% for MR ≥ moderate vs. 58.7% for MR < moderate, p<0.001] and a higher incidence of heart failure readmission at 5-years after TAVI. 11% of patients had progression or persistence of MR ≥ moderate at 1-year after TAVI, which was also associated with reduced survival. On multivariable logistic regression, increasing age, women, lower ejection fraction, prior acute coronary syndrome, concomitant aortic insufficiency ≥ moderate, low-flow low-gradient AS, pulmonary hypertension, baseline tricuspid regurgitation ≥ moderate, and lower mean pre-TAVI aortic transvalvular pressure gradient were associated with progression or persistence of MR ≥ moderate at 1-year after TAVI, while procedural variables and post-procedural complications were not. CONCLUSIONS: Significant MR before and after TAVI was associated with reduced survival. While various clinical variables were associated with significant MR after TAVI, peri-procedural variables were not. Evolution of MR must be carefully surveilled after TAVI, and more data are needed to establish guidelines for managing mixed AS and MR.

Extended Duration of Impella 5.5 Support Does Not Adversely Impact Outcomes Following Heart Transplantation: A National Registry Analysis.

Prior studies assessing the effects of Impella 5.5 support duration on posttransplant outcomes have been limited to single-center case reports and series. This study evaluates the impact of Impella 5.5 support duration on outcomes following heart transplantation using the United Network for Organ Sharing database. Adult heart transplant recipients who were directly bridged to primary isolated heart transplantation with Impella 5.5 were included. The cohort was stratified into two groups based on the duration of Impella support: less than or equal to 14 and greater than 14 days. The primary outcome was 90 day posttransplant survival. Propensity score matching was performed. Sub-analysis was conducted to evaluate the impact of greater than 30 days of Impella support on 90 day survival. Three hundred thirty-two recipients were analyzed. Of these, 212 recipients (63.9%) were directly bridged to heart transplantation with an Impella support duration of greater than 14 days. The two groups had comparable 90 day posttransplant survival and complication rates. The comparable posttransplant survival persisted in a propensity score-matched comparison. In the sub-analysis, Impella support duration of greater than or equal to 30 days did not adversely impact 90 day survival. This study demonstrates that extended duration of support with Impella 5.5 as a bridge to transplantation does not adversely impact posttransplant outcomes. Impella 5.5 is a safe and effective bridging modality to heart transplantation.

Evolving Trends and Impact of Waitlist Transfusion on Recipient Outcomes Following Heart Transplantation.

BACKGROUND: This study evaluates the clinical trends, risk factors, and impact of waitlist blood transfusion on outcomes following isolated heart transplantation. METHODS: The UNOS registry was queried to identify adult recipients from January 1, 2014, to June 30, 2022. The recipients were stratified into two groups depending on whether they received a blood transfusion while on the waitlist. The incidence of waitlist transfusion was compared before and after the 2018 allocation policy change. The primary outcome was survival. Propensity score-matching was performed. Multivariable logistic regression was performed to identify predictors of waitlist transfusion. A sub-analysis was performed to evaluate the impact of waitlist time on waitlist transfusion. RESULTS: From the 21 926 recipients analyzed in this study, 4201 (19.2%) received waitlist transfusion. The incidence of waitlist transfusion was lower following the allocation policy change (14.3% vs. 23.7%, p < 0.001). The recipients with waitlist transfusion had significantly reduced 1-year posttransplant survival (88.8% vs. 91.9%, p < 0.001) compared to the recipients without waitlist transfusion in an unmatched comparison. However, in a propensity score-matched comparison, the two groups had similar 1-year survival (90.0% vs. 90.4%, p = 0.656). Multivariable analysis identified ECMO, Impella, and pretransplant dialysis as strong predictors of waitlist transfusion. In a sub-analysis, the odds of waitlist transfusion increased nonlinearly with longer waitlist time. CONCLUSION: There is a lower incidence of waitlist transfusion among transplant recipients under the 2018 allocation system. Waitlist transfusion is not an independent predictor of adverse posttransplant outcomes but rather a marker of the patient's clinical condition. ECMO, Impella, and pretransplant dialysis are strong predictors of waitlist transfusion.

Six-Year Outcomes of Total Arch Replacement vs Debranching With TEVAR for Aortic Arch Pathologies: Meta-Analysis of Kaplan-Meier-Derived Data From Propensity Score-Matched Studies.

BACKGROUND: Total arch replacement (TAR) and debranching plus thoracic endovascular aortic repair (TEVAR) serve as significant therapeutic options for aortic arch pathologies. It remains unclear whether one of these approaches should be considered preferable. Our study aimed to compare the long-term outcomes of these 2 approaches. METHODS: We carried out a pooled meta-analysis of time-to-event data extracted from studies published by December 2023. Eligibility criteria included populations with any aortic arch pathology who underwent debranching plus TEVAR or TAR, propensity score-matched (PSM) studies (prospective/retrospective; single-center/multicentric), and the outcomes included follow-up for overall survival/mortality and/or reinterventions. RESULTS: Eleven PSM studies met our eligibility criteria, including a total of 1142 patients (571 matched pairs). We did not observe any statistically significant difference in the risk of all-cause death between the groups (hazard ratio [HR]=1.20, 95% confidence interval [CI]=0.91-1.56, p=0.202), but patients who underwent TAR had a significantly lower risk of late aortic reinterventions compared with patients who underwent debranching plus TEVAR (HR=0.38, 95% CI=0.23-0.64, p<0.001). Our meta-regression analyses for all-cause mortality identified statistically significant coefficients for age (coefficient=-0.047; p=0.012) and type A aortic dissections (coefficient=0.012; p=0.010). CONCLUSIONS: Debranching plus TEVAR and TAR demonstrate no statistically significant differences in terms of survival in patients with aortic arch pathologies, but TAR is associated with lower risk of late aortic reinterventions over time. Although older patients may benefit more from debranching plus TEVAR rather than from TAR, patients with dissections may benefit more from TAR. CLINICAL IMPACT: Although the 2 strategies seem to be equally valuable in terms of survival, total aortic arch replacement (when compared with debranching plus TEVAR to treat patients with aortic arch pathologies) is associated with reduction of late aortic reinterventions over time in patients with and without aortic dissections. However, we should consider debranching plus TEVAR in older patients as it is associated with lower risk of death in this population. The novelty of our study lies in the fact that, instead of comparing study-level effect estimates, we analyzed the outcomes with reconstructed time-to-event data. This offered us the opportunity of performing our analyses with a mathematically appropriate model which consider events and time; however, these findings might be under the influence of treatment allocation bias.

Donor and Recipient Age Influence Outcomes Following Orthotopic Heart Transplantation in the 2018 US Heart Allocation System.

BACKGROUND: This study evaluates the interaction of donor and recipient age with outcomes following heart transplantation under the 2018 heart allocation system. METHODS: The United Network for Organ Sharing registry was queried to analyze adult primary isolated orthotopic heart transplant recipients and associated donors from August 18, 2018, to June 30, 2021. Both recipient and donor cohorts were grouped according to age: <65 and ≥65 y for recipients and <50 and ≥50 y for donors. The primary outcome was survival. Subanalyses were performed to evaluate the impact of donor age. RESULTS: A total of 7601 recipients and 7601 donors were analyzed. Of these, 1584 recipients (20.8%) were ≥65 y old and 560 donors (7.4%) were ≥50 y old. Compared with recipients <65, recipients ≥65 had decreased 1-y (88.8% versus 92.3%) and 2-y (85.1% versus 88.5%) survival rates (P < 0.001). The association of recipient age ≥65 with lower survival persisted after adjusting for potential cofounders (hazard ratio, 1.38; 95% confidence interval, 1.18-1.61; P < 0.001). Recipients <65 with donors ≥50 had comparable 1-y and 2-y survival rates to recipients <65 with donors <50 (P =0.997). Conversely, transplantation of older allografts was associated with lower 1-y (84.2% versus 89.4%) and 2-y (79.5% versus 85.8%) survival rates in recipients ≥65 (P = 0.025). CONCLUSIONS: Recipient age ≥65 continues to be associated with worse survival following heart transplantation in the 2018 heart allocation system compared with younger recipients. Donors ≥50 may be acceptable among recipients <65 with comparable outcomes. However, careful donor age selection should be considered for recipients ≥65, as the use of younger donor allografts appears to improve posttransplantation survival.

Early Glasgow Coma Scale Score and Prediction of Traumatic Brain Injury: A Secondary Analysis of Three Harmonized Prehospital Randomized Clinical Trials.

OBJECTIVES: The prehospital prediction of the radiographic diagnosis of traumatic brain injury (TBI) in hemorrhagic shock patients has the potential to promote early therapeutic interventions. However, the identification of TBI is often challenging and prehospital tools remain limited. While the Glasgow Coma Scale (GCS) score is frequently used to assess the extent of impaired consciousness after injury, the utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is poorly understood. METHODS: We performed a post-hoc, secondary analysis utilizing data derived from three randomized prehospital clinical trials: the Prehospital Air Medical Plasma trial (PAMPER), the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport trial (STAAMP), and the Pragmatic Prehospital Type O Whole Blood Early Resuscitation (PPOWER) trial. Patients were dichotomized into two cohorts based on the presence of TBI and then further stratified into three groups based on prehospital GCS score: GCS 3, GCS 4-12, and GCS 13-15. The association between prehospital GCS score and clinical documentation of TBI was assessed. RESULTS: A total of 1,490 enrolled patients were included in this analysis. The percentage of patients with documented TBI in those with a GCS 3 was 59.5, 42.4% in those with a GCS 4-12, and 11.8% in those with a GCS 13-15. The positive predictive value (PPV) of the prehospital GCS score for the diagnosis of TBI is low, with a GCS of 3 having only a 60% PPV. Hypotension and prehospital intubation are independent predictors of a low prehospital GCS. Decreasing prehospital GCS is strongly associated with higher incidence or mortality over time, irrespective of the diagnosis of TBI. CONCLUSIONS: The ability to accurately predict the presence of TBI in the prehospital phase of care is essential. The utility of the GCS scores in the early prehospital phase of care to predict TBI in patients with severe injury and concomitant shock is limited. The use of novel scoring systems and improved technology are needed to promote the accurate early diagnosis of TBI.

Characterization of adverse events in injured patients at risk of hemorrhagic shock: a secondary analysis of three harmonized prehospital randomized clinical trials.

Background: The reporting of adverse events (AEs) is required and well defined in the execution of clinical trials, but is poorly characterized particularly in prehospital trials focusing on traumatic injury. In the setting of prehospital traumatic injury trials, no literature currently exists analyzing the clinical implications of AEs and their associations with mortality and morbidity. We sought to analyze AEs from three prehospital hemorrhagic shock trials and characterize their time course, incidence, severity, associated clinical outcomes, and relatedness. Methods: We performed a secondary analysis of three prehospital randomized clinical trials. We analyzed AEs at both the patient level as well as the individual AE level. We categorized patients who had no AEs, a single documented AE and those with multiple events (>1 AE). We characterized AE timing, severity, relatedness and attributable mortality outcomes. Results: We included 1490 patients from the three harmonized clinical trials, with 299 (20.1%) individual patients having at least a single AE documented with 529 AEs documented overall as a proportion of patients had multiple events. Over 44% of patients had a death-related misclassified AE. Patients with at least a single documented AE had a significantly higher 28-day mortality (log-rank χ2=81.27, p<0.001) compared with those without an AE documented. Patients with a single AE had a significant higher mortality than those with multiple AEs, potentially due to survival bias (log-rank χ2=11.80, p=0.006). When relatedness of each individual AE was characterized, over 97% of AEs were classified as 'definitely not related' or 'probably not related' to the intervention. Conclusions: AEs in hemorrhagic shock trials are common, occur early and are associated with mortality and survival bias. The potential for inaccurate reporting exists, and education and training remain essential for appropriate treatment arm comparison. The current results have important relevance to injury-related clinical trials. Trial registration numbers: NCT01818427, NCT02086500 and NCT03477006. Level of evidence: II.

Long-Term Outcomes of Tricuspid Valve Replacement With Mechanical Versus Tissue Valves: Meta-Analysis of Reconstructed Time-to-Event Data.

Tricuspid valve replacement (TVR) with mechanical versus tissue valves remains a controversial subject. To evaluate the long-term effects of types of valves on patient-relevant outcomes, we performed a systematic review with meta-analysis of reconstructed time-to-event data of studies published by March 15, 2024 (according to referred the Reporting Items for Systematic Reviews and Meta-analyses guidelines). A total of 21 studies met our eligibility criteria and included 7,166 patients (mechanical: 2,495 patients, 34.8%). Patients who underwent mechanical TVR had a lower risk of death than those who received a tissue valve (hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.70 to 0.84, p <0.001). Mechanical TVR was associated with lifetime gain, as evidenced by the restricted mean survival time, which was 2.2 years longer in patients who underwent TVR with mechanical valves (12.4 vs 10.2 years, p <0.001). Our landmark analysis for reoperations revealed the following: from the time point 0 to 7 years, we found no difference in the risk of reoperation between mechanical and tissues valves (HR 0.98, 95% CI 0.60 to 1.61, p = 0.946); however, from the time point 7 years onward, we found that mechanical TVR had a lower risk of reoperation in the follow-up (HR 0.24, 95% CI 0.08 to 0.72, p = 0.001). The meta-regression analysis demonstrated a modulating effect of atrial fibrillation on the association between mechanical valves and mortality; the HRs for all-cause death tended to decrease in the presence of populations with a larger proportion of atrial fibrillation (p = 0.018). In conclusion, our results suggest that TVR with mechanical valves, whenever considered clinically reasonable and accepted by patients as an option, can offer a better long-term survival and lower risk of reoperation in the long run.

Phase-specific survival after endovascular versus open surgical repair of descending thoracic aortic aneurysm.

INTRODUCTION: Thoracic endovascular aortic repair (TEVAR) has gained preference over open surgical repair (OSR) as the intervention of choice for patients with descending thoracic aortic aneurysm (DTA). This study aimed to compare the outcomes of patients with DTA undergoing OSR and TEVAR with contemporary findings. EVIDENCE ACQUISITION: A comprehensive search of MEDLINE and EMBASE databases was conducted to identify relevant randomized controlled trials or studies utilizing propensity-score analysis or reporting risk-adjusted outcomes. The search was performed up until March 2023. EVIDENCE SYNTHESIS: Eight studies met the inclusion criteria, including 4 studies using propensity-score matching and four studies reporting risk-adjusted outcomes, comprising 14,873 patients with DTA undergoing OSR (N.=10,882) and TEVAR (N.=3991). Operative mortality was similar between the two interventions (odds ratio 0.92, 95% CI 0.70-1.21, P=0.57, I2=0%). However, overall long-term mortality was significantly higher after TEVAR compared to OSR (Hazard Ratio [HR] 1.30, 95% CI 1.05-1.59, P=0.01, I2=0%). Phase-specific analysis revealed comparable risks of mortality within 1 year and between one and two years after interventions, while the risk of mortality was significantly higher after TEVAR compared to OSR beyond two years (HR 1.77, 95% CI, 1.19-2.63, P=0.01. I2=0%). CONCLUSIONS: This study demonstrated comparable operative mortality between OSR and TEVAR, but higher long-term mortality associated with TEVAR in patients with DTA. The phase-specific analysis highlighted the survival advantage of OSR beyond 2 years. These findings suggest a need for reconsidering OSR indications in the management of DTA.

Mechanism matters: mortality and endothelial cell damage marker differences between blunt and penetrating traumatic injuries across three prehospital clinical trials.

Injury mechanism is an important consideration when conducting clinical trials in trauma. Mechanisms of injury may be associated with differences in mortality risk and immune response to injury, impacting the potential success of the trial. We sought to characterize clinical and endothelial cell damage marker differences across blunt and penetrating injured patients enrolled in three large, prehospital randomized trials which focused on hemorrhagic shock. In this secondary analysis, patients with systolic blood pressure < 70 or systolic blood pressure < 90 and heart rate > 108 were included. In addition, patients with both blunt and penetrating injuries were excluded. The primary outcome was 30-day mortality. Mortality was characterized using Kaplan-Meier and Cox proportional-hazards models. Generalized linear models were used to compare biomarkers. Chi squared tests and Wilcoxon rank-sum were used to compare secondary outcomes. We characterized data of 696 enrolled patients that met all secondary analysis inclusion criteria. Blunt injured patients had significantly greater 24-h (18.6% vs. 10.7%, log rank p = 0.048) and 30-day mortality rates (29.7% vs. 14.0%, log rank p = 0.001) relative to penetrating injured patients with a different time course. After adjusting for confounders, blunt mechanism of injury was independently predictive of mortality at 30-days (HR 1.84, 95% CI 1.06-3.20, p = 0.029), but not 24-h (HR 1.65, 95% CI 0.86-3.18, p = 0.133). Elevated admission levels of endothelial cell damage markers, VEGF, syndecan-1, TM, S100A10, suPAR and HcDNA were associated with blunt mechanism of injury. Although there was no difference in multiple organ failure (MOF) rates across injury mechanism (48.4% vs. 42.98%, p = 0.275), blunt injured patients had higher Denver MOF score (p < 0.01). The significant increase in 30-day mortality and endothelial cell damage markers in blunt injury relative to penetrating injured patients highlights the importance of considering mechanism of injury within the inclusion and exclusion criteria of future clinical trials.

Missingness matters: a secondary analysis of thromboelastography measurements from a recent prehospital randomized tranexamic acid clinical trial.

Background: Tranexamic acid (TXA) has been hypothesized to mitigate coagulopathy in patients after traumatic injury. Despite previous prehospital clinical trials demonstrating a TXA survival benefit, none have demonstrated correlated changes in thromboelastography (TEG) parameters. We sought to analyze if missing TEG data contributed to this paucity of findings. Methods: We performed a secondary analysis of the Study of Tranexamic Acid During Air Medical and Ground Prehospital Transport Trial. We compared patients that received TEG (YES-TEG) and patients unable to be sampled (NO-TEG) to analyze subgroups in which to investigate TEG differences. TEG parameter differences across TXA intervention arms were assessed within subgroups disproportionately present in the NO-TEG relative to the YES-TEG cohort. Generalized linear models controlling for potential confounders were applied to findings with p<0.10 on univariate analysis. Results: NO-TEG patients had lower prehospital systolic blood pressure (SBP) (100 (78, 140) vs 125 (88, 147), p<0.01), lower prehospital Glascow Coma Score (14 (3, 15) vs 15 (12, 15), p<0.01), greater rates of prehospital intubation (39.4% vs 24.4%, p<0.01) and greater mortality at 30 days (36.4% vs 6.8%, p<0.01). NO-TEG patients had a greater international normalized ratio relative to the YES-TEG subgroup (1.2 (1.1, 1.5) vs 1.1 (1.0, 1.2), p=0.04). Within a severe prehospital shock cohort (SBP<70), TXA was associated with a significant decrease in clot lysis at 30 min on multivariate analysis (ß=-27.6, 95% CI (-51.3 to -3.9), p=0.02). Conclusions: Missing data, due to the logistical challenges of sampling certain severely injured patients, may be associated with a lack of TEG parameter changes on TXA administration in the primary analysis. Previous demonstration of TXA's survival benefit in patients with severe prehospital shock in tandem with the current findings supports the notion that TXA acts at least partially by improving clot integrity. Level of evidence: Level II.

Lung Transplantation Outcomes in Recipients Aged 70 Years or Older and the Impact of Center Volume.

OBJECTIVE: To evaluate trends and outcomes of lung transplants (LTx) in recipients ≥ 70 years. METHODS: We performed a retrospective analysis of the UNOS database identifying all patients undergoing LTx (May 2005-December 2022). Baseline characteristics and postoperative outcomes were compared by age (<70 years, ≥70 years) and center volume. Kaplan-Meier analyses were performed with pairwise comparisons between subgroups. RESULTS: 34,957 patients underwent LTx, of which 3236 (9.3%) were ≥70 years. The rate of LTx in recipients ≥ 70 has increased over time, particularly in low-volume centers (LVCs); consequently, high-volume centers (HVCs) and LVCs perform similar rates of LTx for recipients ≥ 70. Recipients ≥ 70 had higher rates of receiving from donor after circulatory death lungs and of extended donor criteria. Recipients ≥ 70 were more likely to die of cardiovascular diseases or malignancy, while recipients < 70 of chronic primary graft failure. Survival time was shorter for recipients ≥ 70 compared to recipients < 70 old (hazard ratio (HR): 1.36, 95% confidence interval (CI): 1.28-1.44, p < 0.001). HVCs were associated with a survival advantage in recipients < 70 (HR: 0.91, 95% CI: 0.88-0.94, p < 0.001); however, in recipients ≥ 70, survival was similar between HVCs and LVCs (HR: 1.11, 95% CI: 0.99-1.25, p < 0.08). HVCs were more likely to perform a bilateral LTx (BLT) for obstructive lung diseases compared to LVCs, but there was no difference in BLT and single LTx likelihood for restrictive lung diseases. CONCLUSIONS: Careful consideration is needed for recipient ≥ 70 selection, donor assessment, and post-transplant care to improve outcomes. Further research should explore strategies that advance perioperative care in centers with low long-term survival for recipients ≥ 70.

Valve-in-valve transcatheter aortic valve replacement versus isolated redo surgical aortic valve replacement.

OBJECTIVE: To compare outcomes of patients undergoing valve-in-valve transcatheter aortic valve replacement (ViV TAVR) versus redo surgical aortic valve replacement (SAVR). METHODS: This was a retrospective study using institutional databases of transcatheter (2013-2022) and surgical (2011-2022) aortic valve replacements. Patients who underwent ViV TAVR were compared with patients who underwent redo isolated SAVR. Clinical and echocardiographic outcomes were analyzed. Kaplan-Meier survival estimation and Cox regression were performed. Cumulative incidence functions were generated for heart failure readmissions. RESULTS: A total of 4200 TAVRs and 2306 isolated SAVRs were performed. Of these, there were 198 patients who underwent ViV TAVR and 147 patients who underwent redo SAVR. Operative mortality was 2% in each group, but observed to expected operative mortality in the redo SAVR group was higher than in the ViV TAVR group (1.2 vs 0.32). Those who underwent redo SAVR were more likely to require transfusions and reoperation for bleeding, to have new-onset renal failure requiring dialysis, and to require a permanent pacemaker postoperatively than those in the ViV group. Mean gradient was significantly lower in the redo SAVR group than in the ViV group at 30 days and 1 year. Kaplan-Meier survival estimates at 1 year were comparable, and on multivariable Cox regression, ViV TAVR was not significantly associated with an increased hazard of death compared with redo SAVR (hazard ratio, 1.39; 95% CI, 0.65-2.99; P = .40). Competing-risk cumulative incidence estimates for heart-failure readmissions were higher in the ViV cohort. CONCLUSIONS: ViV TAVR and redo SAVR were associated with comparable mortality. Patients who underwent redo SAVR had lower postoperative mean gradients and greater freedom from heart failure readmissions, but they also had more postoperative complications than the VIV group, despite their lower baseline risk profiles.

Air pollution exposure and social responsiveness in childhood: The cincinnati combined childhood cohorts.

Autism Spectrum Disorder (ASD) affects about 1 in 44 children and environmental exposures may contribute to disease onset. Air pollution has been associated with adverse neurobehavioral outcomes, yet little research has examined its association with autistic-like behaviors. Therefore, our objective was to examine the association between exposure to air pollution, including NO2 and PM2.5, during pregnancy and the first year of life to ASD-like behaviors during childhood. Participants (n = 435) enrolled in the Cincinnati Childhood Allergy and Air Pollution Study and the Health Outcomes and Measures of the Environment Study were included in the analysis. Daily exposures to NO2 and PM2.5 at the residential addresses of participants were estimated using validated spatiotemporal models and averaged to obtain prenatal and first year exposure estimates. ASD-like behaviors were assessed via the Social Responsiveness Scale (SRS) questionnaire at age 12. Linear regression models adjusting for confounders were applied to estimate the association between pollutants and SRS scores. After adjusting for covariates, the association between NO2 and PM2.5 and SRS scores remained positive but were no longer statistically significant. Prenatal and first year exposure to NO2 were associated with total SRS T-scores with an estimated 0.4 point increase (95% CI: -0.7, 1.6) per 5.2 ppb increase in NO2 exposure and 0.7 point (95% CI: -0.3, 1.6) per 4.2 ppb increase in NO2 exposure, respectively. For PM2.5, a 2.6 µg/m3 increase in prenatal exposure was associated with a 0.1 point increase (95% CI: -1.1, 1.4) in SRS Total T-scores and a 1.3 µg/m3 increase first year of life was associated with a 1 point increase (95% CI: -0.2, 2.3). In summary, exposure to NO2 and PM2.5 during pregnancy and the first year of life were not significantly associated with higher autistic-like behaviors measured with SRS scores after adjustment of covariates. Additional research is warranted given prior studies suggesting air pollution contributes to ASD.