Long-term outcomes after aortic root replacement for bicuspid aortic valve-associated aneurysm.

OBJECTIVE: Patients with congenital bicuspid aortic valve often require root replacement. This study aims to describe their long-term rates of mortality and reoperation. METHODS: This is a multicenter retrospective study of 747 patients with bicuspid aortic valve who underwent aortic root replacement for aortic aneurysm between 2004 and 2020. Cumulative incidence curves for aortic valve and aortic reoperations were graphed. A Kaplan-Meier survival curve for the patient cohort was created alongside an age- and sex-matched curve for the US population. Multivariable Cox regression was used to determine characteristics associated with long-term mortality. RESULTS: The median age of our cohort was 54 [43-64] years old, and 101 (13.5%) patients were female. In patients with bicuspid aortic valve dysfunction, 274 (36.7%) had aortic insufficiency, 187 (25.0%) had aortic stenosis, and 142 (19.0%) had both. In-hospital mortality occurred in 10 (1.3%) patients. There were 56 aortic valve reoperations and 19 aortic reoperations, with a combined cumulative incidence of 35% (95% confidence interval [CI], 23%-46%) at 15 years. In addition, there was comparable survival between the patient cohort and the age- and sex-matched US population. Age (hazard ratio [HR], 1.04; 95% CI, 1.01-1.06), concomitant CABG (HR, 2.28; 95% CI, 1.29-4.04), and bypass time (HR, 1.01; 95% CI, 1.00-1.01) were associated with increased mortality. CONCLUSIONS: Patients who undergo aortic root replacement with bicuspid aortic valve have an increased rate of aortic reoperation (35%; 95% CI, 23%-46%) while their survival appears to be comparable to the general US population (79%; 95% CI, 73%-87%) at 15 years.

Is surgical risk of aortic arch aneurysm repair underestimated? A novel perspective based on 30-day versus 1-year mortality.

OBJECTIVES: The decision to undergo aortic aneurysm repair balances the risk of operation with the risk of aortic complications. The surgical risk is typically represented by perioperative mortality, while the aneurysmal risk relates to the 1-year risk of aortic events. We investigate the difference in 30-day and 1-year mortality after total arch replacement for aortic aneurysm. METHODS: This was an international two-centre study of 456 patients who underwent total aortic arch replacement for aneurysm between 2006 and 2020. Our primary end-point of interest was 1-year mortality. Our secondary analysis determined which variables were associated with 1-year mortality. RESULTS: The median age of patients was 65.4 years (interquartile range 55.1-71.1) and 118 (25.9%) were female. Concomitantly, 91 (20.0%) patients had either an aortic root replacement or aortic valve procedure. There was a drop in 1-year (81%, 95% confidence interval (CI) 78-85%) survival probability compared to 30-day (92%, 95% CI 90-95%) survival probability. Risk hazards regression showed the greatest risk of mortality in the first 4 months after discharge. Stroke [hazard ratio (HR) 2.54, 95% CI (1.16-5.58)], renal failure [HR 3.59 (1.78-7.25)], respiratory failure [HR 3.65 (1.79-7.42)] and reoperation for bleeding [HR 2.97 (1.36-6.46)] were associated with 1-year mortality in patients who survived 30 days. CONCLUSIONS: There is an increase in mortality up to 1 year after aortic arch replacement. This increase is prominent in the first 4 months and is associated with postoperative complications, implying the influence of surgical insult. Mortality beyond the short term may be considered in assessing surgical risk in patients who are undergoing total arch replacement.

Significance of isolated postoperative atrial fibrillation in thoracic aortic aneurysm repair.

OBJECTIVE: Although postoperative atrial fibrillation has been shown to be associated with worse survival after thoracic aortic surgery, its effect on outcomes independently from other postoperative complications is not well understood. METHODS: This is a single-center retrospective study of patients who underwent open thoracic aortic aneurysm repair between March 2005 and March 2021. Postoperative atrial fibrillation was defined as new-onset atrial fibrillation that developed during the index hospital stay. Patients with preoperative atrial fibrillation were excluded. Postoperative major complications included reoperation for bleeding, respiratory failure, acute renal failure, and stroke. Variables associated with postoperative atrial fibrillation were analyzed with multivariable regression. Survival of patients without major complications was compared between patients without atrial fibrillation and patients with postoperative atrial fibrillation after propensity score matching for baseline and intraoperative characteristics. RESULTS: Of 1454 patients, 520 (35.8%) were observed to have postoperative atrial fibrillation. Patients with postoperative atrial fibrillation had a higher rate of postoperative major complications than those without atrial fibrillation (20.2% vs 12.2%, P < .001). Ten-year survival was 82.0% in patients with postoperative atrial fibrillation and 87.0% in patients without atrial fibrillation (P = .008). In the cohort of patients without complications, 10-year survival was similar between patients with and without postoperative atrial fibrillation after propensity score matching (83.6% vs 83.8%, P = .75). CONCLUSIONS: Postoperative atrial fibrillation is common after open proximal thoracic aortic aneurysm repair. Although development of major postoperative complications is associated with postoperative atrial fibrillation and decreased long-term survival, isolated postoperative atrial fibrillation does not appear to influence long-term survival.

Reintervention after valve-sparing aortic root replacement: A comprehensive analysis of 781 David V procedures.

OBJECTIVE: Studies of reintervention after valve-sparing aortic root replacement (VSRR) are limited by sample size and failure to evaluate all types of reinterventions, including distal aorta and transcatheter interventions. In this report, reintervention after VSRR using a large patient cohort was comprehensively analyzed. METHODS: In a series involving 2 academic aortic centers, 781 consecutive patients from 2005 to 2020 undergoing David V VSRR for aortic aneurysm (91%) or dissection (9%) were included. Median age was 50 years, and 23% had a bicuspid aortic valve (AV). Median follow-up was 7.0 years. Open or transcatheter reintervention on the AV, proximal, or distal thoracic aorta was identified. Cumulative incidence was calculated, and subdistribution hazard models identified factors associated with reintervention. Time-dependent incidence of reintervention was plotted using risk-hazard functions. RESULTS: Sixty-eight reinterventions (57 open, 11 transcatheter) were performed. Reinterventions were divided by indication into degenerative AV (n = 26, including 1 transcatheter aortic valve replacement), endocarditis (n = 11), proximal aorta (n = 8), and distal aorta (n = 23, including 10 thoracic endovascular aortic repairs). Risk of reintervention for endocarditis peaked 1 to 3 years after VSRR, whereas other indications had stable, low rates of occurrence throughout the follow-up period. The cumulative incidence of reintervention was 12.5% whereas the cumulative incidence of AV reintervention was 7.0% at 10 years and was associated with residual postoperative aortic insufficiency. In-hospital mortality after reintervention was 3%. CONCLUSIONS: Reintervention rates after VSRR are relatively low in long-term follow-up and can be performed with acceptable operative risk. The majority of reinterventions are performed for indications other than AV degeneration, with the timing of reintervention varying by the specific clinical indication.

Valve-sparing aortic root replacement versus composite valve graft with bioprosthesis in patients under age 50.

BACKGROUND: Although the unique risks of implanting a prosthetic valve after aortic valve (AV) surgery in young patients are well established, studies of aortic root replacement (ARR) are lacking. We investigated long-term outcomes after valve-sparing root replacement (VSRR) versus the use of a composite valve graft with bioprosthesis (b-CVG) in patients age <50 years. METHODS: A total of 543 patients age <50 years underwent VSRR (n = 335) or b-CVG (n = 208) between 2004 and 2021 from 2 aortic centers, excluding those with dissection or endocarditis. Endpoints included mortality over time, reoperative aortic valve replacement (AVR), and development of greater than moderate aortic insufficiency (AI) or aortic stenosis (AS). Fine and Gray competing risk regression was used to compare the risk of reintervention. Propensity score matching (PSM) balanced patient comorbidities, and landmark analysis isolated outcomes beginning 4 years postoperatively. RESULTS: Compared with VSRR, b-CVG was associated with lower 12-year survival (88.6% vs 92.9%; P = .036) and a higher rate of AV reintervention (37.6% vs 12.0%; P = .018). After PSM, survival was similar in the 2 arms (93.4% for b-CVG vs 93.0% for VSRR; P = .72). However, both Fine and Gray multivariable risk regression and PSM showed that b-CVG was independently associated with AV reintervention at >4 years postoperatively (Fine and Gray: subdistribution hazard ratio, 4.3 [95% confidence interval, 1.8-10.2; P = .001]; PSM: 35.7% for b-CVG versus 14.3% for VSRR; P = .024]). PSM rates of greater than moderate AI/AS at 10 years were more than 2-fold greater in the b-CVG arm compared with the VSRR arm (37.1% vs 15.9%; P = .571). CONCLUSIONS: b-CVG in young patients is associated with early valvular degeneration, with increasing rates of reoperative AVR occurring even within 10 years. In contrast, VSRR is durable with excellent survival. In eligible young patients, every effort should be made to retain the native AV.

Bicuspid aortic valve durability with valve-sparing aortic root replacement: comparison to tricuspid valve.

OBJECTIVES: Outcomes beyond 10 years for David V valve-sparing aortic root replacement (VSARR) in bicuspid aortic valve (BAV) patients have yet to be explored. We investigated long-term outcomes after BAV VSARR compared to VSARR for tricuspid aortic valve (TAV) patients. METHODS: A total of 677 patients with BAV (n = 171) and TAV (n = 506) underwent VSARR between 2005 and 2020 from 2 aortic centres, excluding those with dissection, endocarditis, stenosis or prior aortic valve (AV) surgery. Multivariable Cox regression compared adjusted survival over a 12-year period. Fine and Gray competing risk regression compared risk and cumulative incidence of reoperation/reintervention. Propensity score matching created balanced groups, and landmark analysis isolated outcomes beginning 4 years postoperatively. Finally, longitudinal mixed modelling assessed AV deterioration on echocardiogram. RESULTS: No difference was observed in 12-year survival of BAV versus TAV (propensity score matching 92.0% vs 89.9%, P = 0.97; multivariable hazard ratio 0.76, 95% confidence interval 0.34-1.69, P = 0.51). Adjusted 12-year cumulative incidence and risk of AV and/or proximal aorta reoperation/reintervention were not observed to be different (15.7% BAV vs 5.7% TAV, P = 0.37; subdistribution hazard ratio 1.54, 95% confidence interval 0.60-3.94, P = 0.36); however, landmark analysis showed increased incidence of late reoperation/reintervention in BAV versus TAV (11.7% vs 0.0%, P = 0.04). BAV was not associated with AV deterioration over time (BAV coefficient ± standard error: 0 ± 0.30, P = 1). CONCLUSIONS: VSARR for BAV patients has excellent 12-year survival and low reoperation/reintervention rates, which were not observed to be different from TAV patients. However, higher incidence of reoperation/reintervention was observed in the late years after BAV VSARR. Our study provides key information for surgical consultation of patients with bicuspid aortopathy.

Adult Trauma Patients with Autism Spectrum Disorder: A Case-Control Study to Evaluate Disparities After Injury.

BACKGROUND: Adult trauma patients with autism spectrum disorder (ASD) may have distinct care needs that have not been previously described. We hypothesized that due to differences in clinical care and disposition issues, injured adults with ASD would have increased lengths of stay, higher mortality, and increased rates of complications compared to adults without ASD. METHODS: The Pennsylvania Trauma Outcomes Study database was queried from 2010-2018 for trauma patients with ASD. Case-control matching was performed for two controls per ASD patient accounting for age, gender, injury mechanism, and injury severity score. Primary outcomes included length of stay, mortality, and complication rate. Univariate analysis compared presentation and clinical care between the two groups. Multivariate regression and Kaplan-Meier curves modeled length of stay. Significance was defined as p < 0.05. RESULTS: A total of 185 patients with ASD were matched to 370 controls. Age (mean +/- standard deviation) was 33.4 +/- 16.5 years. Gender was 81.1% male. Mechanisms were 88.1% blunt, 5.9% penetrating, and 5.9% burns. Significant clinical differences identified in patients with ASD vs. case-controls included presenting verbal GCS (median [IQR]) (5 [2] vs. 5 [0], p < 0.01), proportion of patients intubated at presentation (20.0% vs. 13.0%, p = 0.031), and hospital length of stay (4 [6] days vs. 3 [4] days, p = 0.002). Adult patients with ASD were less likely to be discharged home and more often discharged to a skilled nursing facility (p < 0.01). There were no differences in mortality, rates of complications, imaging, or operations. Multivariate regression analysis controlling for demographic and clinical differences revealed the diagnosis of ASD independently contributed 3.13 days (95% Confidence Interval: 1.85 to 4.41 days) to injured adults' length of stay. Kaplan-Meier curves showed injured patients with ASD were less likely to be discharged than case-controls starting from time of admission (log rank test, p < 0.001). CONCLUSIONS: This statewide analysis suggests injured patients with ASD have increased lengths of stay without other clinical or outcome differences. Given significant differences in discharge destination, these findings support early involvement of a multidisciplinary care collaborative. Further research is needed to identify factors that contribute to disparities in care for adults with ASD.

A Diet Mimicking Fasting Promotes Regeneration and Reduces Autoimmunity and Multiple Sclerosis Symptoms.

Dietary interventions have not been effective in the treatment of multiple sclerosis (MS). Here, we show that periodic 3-day cycles of a fasting mimicking diet (FMD) are effective in ameliorating demyelination and symptoms in a murine experimental autoimmune encephalomyelitis (EAE) model. The FMD reduced clinical severity in all mice and completely reversed symptoms in 20% of animals. These improvements were associated with increased corticosterone levels and regulatory T (Treg) cell numbers and reduced levels of pro-inflammatory cytokines, TH1 and TH17 cells, and antigen-presenting cells (APCs). Moreover, the FMD promoted oligodendrocyte precursor cell regeneration and remyelination in axons in both EAE and cuprizone MS models, supporting its effects on both suppression of autoimmunity and remyelination. We also report preliminary data suggesting that an FMD or a chronic ketogenic diet are safe, feasible, and potentially effective in the treatment of relapsing-remitting multiple sclerosis (RRMS) patients (NCT01538355).

A Periodic Diet that Mimics Fasting Promotes Multi-System Regeneration, Enhanced Cognitive Performance, and Healthspan.

Prolonged fasting (PF) promotes stress resistance, but its effects on longevity are poorly understood. We show that alternating PF and nutrient-rich medium extended yeast lifespan independently of established pro-longevity genes. In mice, 4 days of a diet that mimics fasting (FMD), developed to minimize the burden of PF, decreased the size of multiple organs/systems, an effect followed upon re-feeding by an elevated number of progenitor and stem cells and regeneration. Bi-monthly FMD cycles started at middle age extended longevity, lowered visceral fat, reduced cancer incidence and skin lesions, rejuvenated the immune system, and retarded bone mineral density loss. In old mice, FMD cycles promoted hippocampal neurogenesis, lowered IGF-1 levels and PKA activity, elevated NeuroD1, and improved cognitive performance. In a pilot clinical trial, three FMD cycles decreased risk factors/biomarkers for aging, diabetes, cardiovascular disease, and cancer without major adverse effects, providing support for the use of FMDs to promote healthspan.