Implications of Bicuspid Aortic Valve Disease and Aortic Stenosis/Insufficiency as Risk Factors for Thoracic Aortic Aneurysm.

Bicuspid Aortic Valves (BAV) are associated with an increased incidence of thoracic aortic aneurysms (TAA). TAA are a common aortic pathology characterized by enlargement of the aortic root and/or ascending aorta, and may become life threatening when left untreated. Typically occurring as the sole pathology in a patient, TAA are largely asymptomatic. However, in some instances, they are accompanied by aortic valve (AV) diseases: either congenital BAV or acquired in the form of Aortic Insufficiency (AI) or aortic stenosis (AS). When TAA are associated with aortic valve disease, determining an accurate and predictable prognosis becomes especially challenging. Patients with AV disease and concomitant TAA lack a widely accepted diagnostic approach, one that integrates our knowledge on aortic valve pathophysiology and encompasses multi-modality imaging approaches. This review summarizes the most recent scientific knowledge regarding the association between AV diseases (BAV, AI, AS) and ascending aortopathies (dilatation, aneurysm, and dissection). We aimed to pinpoint the gaps in monitoring practices and prediction of disease progression in TAA patients with concomitant AV disease. We propose that a morphological and functional analysis of the AV with multi-modality imaging should be included in aortic surveillance programs. This strategy would allow for improved risk stratification of these patients, and possibly new AV phenotypic-specific guidelines with more vigilant surveillance and earlier prophylactic surgery to improve patient outcomes.

Dynamical Approach to the Jamming Problem.

A simple dynamical model, biased random organization (BRO), appears to produce configurations known as random close packing (RCP) as BRO's densest critical point in dimension d=3. We conjecture that BRO likewise produces RCP in any dimension; if so, then RCP does not exist in d=1-2 (where BRO dynamics lead to crystalline order). In d=3-5, BRO produces isostatic configurations and previously estimated RCP volume fractions 0.64, 0.46, and 0.30, respectively. For all investigated dimensions (d=2-5), we find that BRO belongs to the Manna universality class of dynamical phase transitions by measuring critical exponents associated with the steady-state activity and the long-range density fluctuations. Additionally, BRO's distribution of near contacts (gaps) displays behavior consistent with the infinite-dimensional theoretical treatment of RCP when d≥4. The association of BRO's densest critical configurations with random close packing implies that RCP's upper-critical dimension is consistent with the Manna class d_{uc}=4.

Coupled Dynamical Phase Transitions in Driven Disk Packings.

Under the influence of oscillatory shear, a monolayer of frictional granular disks exhibits two dynamical phase transitions: a transition from an initially disordered state to an ordered crystalline state and a dynamic active-absorbing phase transition. Although there is no reason a priori for these to be at the same critical point, they are. The transitions may also be characterized by the disk trajectories, which are nontrivial loops breaking time-reversal invariance.

Model-Free Measurement of Local Entropy Production and Extractable Work in Active Matter.

Time-reversal symmetry breaking and entropy production are universal features of nonequilibrium phenomena. Despite its importance in the physics of active and living systems, the entropy production of systems with many degrees of freedom has remained of little practical significance because the high dimensionality of their state space makes it difficult to measure. Here we introduce a local measure of entropy production and a numerical protocol to estimate it. We establish a connection between the entropy production and extractability of work in a given region of the system and show how this quantity depends crucially on the degrees of freedom being tracked. We validate our approach in theory, simulation, and experiments by considering systems of active Brownian particles undergoing motility-induced phase separation, as well as active Brownian particles and E.coli in a rectifying device in which the time-reversal asymmetry of the particle dynamics couples to spatial asymmetry to reveal its effects on a macroscopic scale.

Random Close Packing as a Dynamical Phase Transition.

Sphere packing is an ancient problem. The densest packing is known to be a face-centered cubic (FCC) crystal, with space-filling fraction ϕ_{FCC}=π/sqrt[18]≈0.74. The densest "random packing," random close packing (RCP), is yet ill defined, although many experiments and simulations agree on a value ϕ_{RCP}≈0.64. We introduce a simple absorbing-state model, biased random organization (BRO), which exhibits a Manna class dynamical phase transition between absorbing and active states that has as its densest critical point ϕ_{c_{max}}≈0.64≈ϕ_{RCP} and, like other Manna class models, is hyperuniform at criticality. The configurations we obtain from BRO appear to be structurally identical to RCP configurations from other protocols. This leads us to conjecture that the highest-density absorbing state for an isotropic biased random organization model produces an ensemble of configurations that characterizes the state conventionally known as RCP.

Correlation Lengths in the Language of Computable Information.

Computable information density (CID), the ratio of the length of a losslessly compressed data file to that of the uncompressed file, is a measure of order and correlation in both equilibrium and nonequilibrium systems. Here we show that correlation lengths can be obtained by decimation, thinning a configuration by sampling data at increasing intervals and recalculating the CID. When the sampling interval is larger than the system's correlation length, the data becomes incompressible. The correlation length and its critical exponents are thus accessible with no a priori knowledge of an order parameter or even the nature of the ordering. The correlation length measured in this way agrees well with that computed from the decay of two-point correlation functions g_{2}(r) when they exist. But the CID reveals the correlation length and its scaling even when g_{2}(r) has no structure, as we demonstrate by "cloaking" the data with a Rudin-Shapiro sequence.

Underutilization of Nonopioid Pain Medication in Patients Undergoing Abdominal Aortic Aneurysm Repair.

BACKGROUND: With increased focus on the opioid crisis, it was our goal to describe rates and risk factors for postoperative use of opioids in patients undergoing abdominal aortic aneurysm (AAA) repair as well as identify pain modalities that are underutilized. METHODS: We retrospectively analyzed perioperative analgesic prescriptions for endovascular (EVAR) and open AAA repair between January 1, 2010 and January 1, 2018. Patients' baseline opioid use, demographics, and medical comorbidities were obtained. The EVAR group was further subdivided into percutaneous (pEVAR) and cutdown (cEVAR) groups. Primary outcomes were postoperative and discharge pain medication prescriptions. Relative rates of opioid prescribing were obtained through the electronic medical record and normalized into morphine milligram equivalents (MMEs). RESULTS: Of the 128 patients analyzed in the entire cohort, 21.8% (n = 28) underwent open repair and 78.12% (n = 100) underwent EVAR (46 pEVAR, 54 cEVAR). As expected, open repair had increased postoperative pain reported compared to EVAR (2.67 ± 0.75 vs. 0.96 ± 0.19, P < 0.01). Adjunctive epidural reduced postoperative pain for open repair (0.77 ± 0.48 vs. 3.50 ± 0.96, P < 0.01). EVAR had less postoperative opioid prescriptions compared to open repair (35.0% vs. 77.3%, P < 0.01). In the endovascular group, there was no difference between postoperative opioid prescription based on access, pEVAR versus cEVAR (65.8% vs. 80.1%, P = 0.11). When stratifying patients by number of cutdowns, patients with bilateral cutdown as opposed to a single cutdown received more opioid prescriptions than pEVAR patients (84.44% vs. 65.8%, P = 0.036). Of those receiving opioids, the average MME for open repair was 320.94 mg compared to 28.82 mg for EVAR (P < 0.01). Those undergoing percutaneous repair had significantly less MME use during hospitalization compared to femoral cutdown (17 ± 3.52 vs. 31.90 ± 5.43 mg, P < 0.01). Nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen and ketorolac, were rarely used in the postoperative period for open or EVAR (8.3% vs 1.1%). Percutaneous EVAR patients reported less pain at discharge compared to cEVAR patients (0.18 ± 0.12 vs. 0.88 ± 0.29, P = 0.036). Open and EVAR had comparable low rates of NSAID and acetaminophen prescriptions at discharge. Open patients had longer postoperative length of stay compared to EVAR patients (9.82 ± 1.27 vs. 3.86 ± 0.47, P < 0.01). pEVAR had a shorter length of postoperative course compared to cEVAR (3.2 ± 0.26 vs. 4.12 ± 0.30, P < 0.01). Patients undergoing EVAR with use of pain medications amounting to <20 MME had a significantly shorter length of stay. CONCLUSIONS: This single institutional retrospective study evaluated pain prescription patterns for patients undergoing AAA repair. AAA patients are predominantly treated with opioid pain medications with few adjunctive therapies. Intraoperative epidural and pEVAR may aid in decreasing the total MME used; however, the total number of opioids prescribed is similar for pEVAR and cEVAR despite the difference in approach. Clinicians must consider alternative nonopioid based pain management strategies.

Enhanced hyperuniformity from random reorganization.

Diffusion relaxes density fluctuations toward a uniform random state whose variance in regions of volume [Formula: see text] scales as [Formula: see text] Systems whose fluctuations decay faster, [Formula: see text] with [Formula: see text], are called hyperuniform. The larger [Formula: see text], the more uniform, with systems like crystals achieving the maximum value: [Formula: see text] Although finite temperature equilibrium dynamics will not yield hyperuniform states, driven, nonequilibrium dynamics may. Such is the case, for example, in a simple model where overlapping particles are each given a small random displacement. Above a critical particle density [Formula: see text], the system evolves forever, never finding a configuration where no particles overlap. Below [Formula: see text], however, it eventually finds such a state, and stops evolving. This "absorbing state" is hyperuniform up to a length scale [Formula: see text], which diverges at [Formula: see text] An important question is whether hyperuniformity survives noise and thermal fluctuations. We find that hyperuniformity of the absorbing state is not only robust against noise, diffusion, or activity, but that such perturbations reduce fluctuations toward their limiting behavior, [Formula: see text], a uniformity similar to random close packing and early universe fluctuations, but with arbitrary controllable density.

Noise, Diffusion, and Hyperuniformity.

We consider driven many-particle models which have a phase transition between an active and an absorbing phase. Like previously studied models, we have particle conservation, but here we introduce an additional symmetry-when two particles interact, we give them stochastic kicks which conserve the center of mass. We find that the density fluctuations in the active phase decay in the fastest manner possible for a disordered isotropic system, and we present arguments that the large scale fluctuations are determined by a competition between a noise term which generates fluctuations, and a deterministic term which reduces them. Our results may be relevant to shear experiments and may further the understanding of hyperuniformity which occurs at the critical point.

Exposure to bisphenols and phthalates and association with oxidant stress, insulin resistance, and endothelial dysfunction in children.

BACKGROUND: The health effects of bisphenol A (BPA) and di-(2-ethylhexyl) phthalate (DEHP) have been studied extensively in children. The impact of other chemicals in these two classes has not been investigated as fully. METHODS: We conducted a cross-sectional pilot study of 10-13 y old healthy children. We assessed descriptive, univariable, and multivariable associations of urinary metabolites of bisphenols and phthalates with oxidant stress, insulin resistance, body mass, and endothelial dysfunction. Possible associations with brachial artery distensibility, pulse wave velocity (markers of vascular stiffness), and serum endothelial cell-derived microparticle levels were also assessed. RESULTS: We enrolled 41 participants, 12.1 ± 1.0 y, most of whom were Mexican Americans (42%) or other Hispanics (34%). Increased BPA levels were associated with increased levels of F2-isoprostane (ng/ml) (P = 0.02), with a similar trend for DEHP metabolites. Each log unit increase of high molecular weight (HMW) phthalate metabolites was associated with a 0.550 increase in Homeostatic Model Assessment of insulin resistance (HOMA-IR) units (P = 0.019) and altered circulating levels of activated endothelial cell-derived microparticles (% per ml) (P = 0.026). Bisphenol S (BPS), a replacement for BPA, was associated with increased albumin (mg):creatinine (g) ratio (P = 0.04). Metabolites of HMW phthalates were also associated with decreased brachial artery distensibility (P = 0.047). CONCLUSION: Exposure to bisphenols and phthalates, including a BPA replacement, is associated with increased oxidant stress, insulin resistance, albuminuria, as well as disturbances in vascular function in healthy children.

Hyperuniformity of critical absorbing states.

The properties of the absorbing states of nonequilibrium models belonging to the conserved directed percolation universality class are studied. We find that, at the critical point, the absorbing states are hyperuniform, exhibiting anomalously small density fluctuations. The exponent characterizing the fluctuations is measured numerically, a scaling relation to other known exponents is suggested, and a new correlation length relating to this ordering is proposed. These results may have relevance to photonic band-gap materials.

Silent flocks: constraints on signal propagation across biological groups.

Experiments find coherent information transfer through biological groups on length and time scales distinctly below those on which asymptotically correct hydrodynamic theories apply. We present here a new continuum theory of collective motion coupling the velocity and density fields of Toner and Tu to the inertial spin field recently introduced to describe information propagation in natural flocks of birds. The long-wavelength limit of the new equations reproduces the Toner-Tu theory, while at shorter wavelengths (or, equivalently, smaller damping), spin fluctuations dominate over density fluctuations, and second-sound propagation of the kind observed in real flocks emerges. We study the dispersion relation of the new theory and find that when the speed of second sound is large, a gap in momentum space sharply separates first- from second-sound modes. This gap implies the existence of silent flocks, namely, of medium-sized systems across which information cannot propagate in a linear and underdamped way, either under the form of orientational fluctuations or under that of density fluctuations, making it hard for the group to achieve coordination.

Defect turbulence in a dense suspension of polar, active swimmers.

We study the effects of inertia in dense suspensions of polar swimmers. The hydrodynamic velocity field and the polar order parameter field describe the dynamics of the suspension. We show that a dimensionless parameter R (ratio of the swimmer self-advection speed to the active stress invasion speed [Phys. Rev. X 11, 031063 (2021)2160-330810.1103/PhysRevX.11.031063]) controls the stability of an ordered swimmer suspension. For R smaller than a threshold R_{1}, perturbations grow at a rate proportional to their wave number q. Beyond R_{1} we show that the growth rate is O(q^{2}) until a second threshold R=R_{2} is reached. The suspension is stable for R>R_{2}. We perform direct numerical simulations to characterize the steady-state properties and observe defect turbulence for R

Incidence, risk factors, and long-term outcomes associated with permanent pacemaker implantation after aortic root replacement.

OBJECTIVE: Permanent pacemaker implantation (PPI) after AVR is associated with long-term mortality. However, data regarding PPI after aortic root replacement (ARR) is lacking. Herein we describe the incidence, risk factors, and long-term outcomes of PPI after ARR. METHODS: Consecutive patients undergoing ARR from 2005-2020 were selected after excluding those with endocarditis, Type A dissection, or preoperative PPI. Patients requiring PPI after ARR were identified, along with the indication and timing. Independent factors associated with PPI after ARR were identified and long-term survival was assessed. RESULTS: The incidence of PPI was 3.8% (n=85) among 2240 patients undergoing ARR. PPI was performed a median of 7 days (IQR 5-12) after ARR most commonly for complete heart block (73%). Bicuspid aortic valve (OR 1.89, p=0.02), female gender (OR 1.74, p=0.04), preoperative heart block (OR 2.70, p=0.02), and prior AVR (OR 2.18, p=0.01) were independently associated with PPI while preoperative aortic insufficiency (OR 0.52, p=0.01) and VSRR procedure compared to bio-Bentall (OR 0.40, p=0.01) were protective. Patients requiring PPI after ARR were not at increased risk of operative or long-term mortality compared to patients not requiring PPI (p=0.26), however those undergoing PPI suffered from significantly longer hospital length of stay (13 vs 7 days, p<0.001). CONCLUSIONS: The incidence of PPI after ARR remains low, particularly after VSRR. Preoperative conduction disturbance, prior AVR, and bicuspid AV are all associated with increased risk of PPI. While PPI is associated with longer length of stay, it is not associated with early or late mortality.

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.

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.

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.

Entropic commensurate-incommensurate transition.

The equilibrium properties of a minimal tiling model are investigated. The model has extensive ground state entropy, with each ground state having a quasiperiodic sequence of rows. It is found that the transition from the ground state to the high temperature disordered phase proceeds through a sequence of periodic arrangements of rows, in analogy with the commensurate-incommensurate transition. We show that the effective free energy of the model resembles the Frenkel-Kontorova Hamiltonian, but with temperature playing the role of the strength of the substrate potential, and with the competing lengths not explicitly present in the basic interactions.

Reoperative aortic root replacement for prosthetic aortic valve endocarditis: impact of aortic graft.

OBJECTIVES: Existing aortic graft complicates the surgical management of prosthetic valve endocarditis (PVE); yet, its impact has not been well studied. We compared outcomes of patients with prior aortic valve replacement (AVR) versus aortic surgery plus AVR, who underwent reoperative aortic root replacement (ARR) for PVE of the aortic valve. METHODS: All patients who underwent reoperative ARR for PVE between 2004 and 2021 from 2 aortic centres were included. Two groups were formed based on the presence/absence of aortic graft: prior aortic surgery (AO) and prior AVR (AV) alone. Inverse propensity treatment weighting matched the groups. The Kaplan-Meier method was used to analyse long-term survival, and Fine and Gray model was used to compare the cumulative incidence of reoperation. RESULTS: A total of 130 patients were included (AO n = 59; AV n = 71). After matching, AO patients had increased stroke incidence (12.4% vs 0.9%) and renal failure requiring dialysis (11.5% vs 2.5%). In-hospital mortality was comparable (21.5% AO and 18.6% AV). Survival over 5 years was 68.9% (56.6-83.8%) in AO and 62.7% (48.1-81.7%) in AV (P = 0.70). The cumulative incidence of reoperation was similar [AO 6.3% (0.0-13.2%) vs AV 6.1% (0.0-15.1%), P = 0.69]. CONCLUSIONS: Reoperative ARRs for prosthetic valve/graft endocarditis are high-risk procedures. AO patients had higher incidence of postoperative morbidity versus AV patients. For all patients surviving operative intervention, survival and reoperation rates over 5 years were comparable between groups.