Biologically derived epicardial patch induces macrophage mediated pathophysiologic repair in chronically infarcted swine hearts.

There are nearly 65 million people with chronic heart failure (CHF) globally, with no treatment directed at the pathologic cause of the disease, the loss of functioning cardiomyocytes. We have an allogeneic cardiac patch comprised of cardiomyocytes and human fibroblasts on a bioresorbable matrix. This patch increases blood flow to the damaged heart and improves left ventricular (LV) function in an immune competent rat model of ischemic CHF. After 6 months of treatment in an immune competent Yucatan mini swine ischemic CHF model, this patch restores LV contractility without constrictive physiology, partially reversing maladaptive LV and right ventricular remodeling, increases exercise tolerance, without inducing any cardiac arrhythmias or a change in myocardial oxygen consumption. Digital spatial profiling in mice with patch placement 3 weeks after a myocardial infarction shows that the patch induces a CD45pos immune cell response that results in an infiltration of dendritic cells and macrophages with high expression of macrophages polarization to the anti-inflammatory reparative M2 phenotype. Leveraging the host native immune system allows for the potential use of immunomodulatory therapies for treatment of chronic inflammatory diseases not limited to ischemic CHF.

A Classroom Activity to Increase Student Pharmacists Confidence in Dealing with the Opioid Epidemic.

Objective. To implement and assess the impact of a hybrid flipped-classroom activity designed to increase the motivation and confidence of Doctor of Pharmacy (PharmD) students in addressing the opioid crisis. Methods. Third-professional year student pharmacists were provided with reading material developed by federal agencies and professional pharmacy organizations, as well as Georgia-specific information covering medical amnesty and local resources for opioid-overdose prevention prior to class. They then attended a four-hour classroom session that included hearing a lecture on opioid pharmacology and opioid overdose, viewing training videos, and engaging in extensive discussion. The students voluntarily completed pre- and post-intervention assessments regarding opioid abuse and opioid overdose prevention. Results. Seventy of the 107 third-year students enrolled in the course completed the pre-intervention assessment (65% response rate), and 33 of the 70 completed the post-intervention assessment (47% retention rate). The students exhibited a high baseline motivation to assist in combating the opioid crises, but less confidence in their ability to intervene. Significant increases were seen in areas related to student confidence on the post-intervention assessment. Fewer changes were seen in areas related to student motivation. Conclusion. A "hybrid" flipped classroom activity increased the confidence of student pharmacists in their understanding of the physical and adverse effects of opioids and the application of reversal agents. Increased confidence may support increased intervention.

Arctic sea ice melt leads to atmospheric new particle formation.

Atmospheric new particle formation (NPF) and growth significantly influences climate by supplying new seeds for cloud condensation and brightness. Currently, there is a lack of understanding of whether and how marine biota emissions affect aerosol-cloud-climate interactions in the Arctic. Here, the aerosol population was categorised via cluster analysis of aerosol size distributions taken at Mt Zeppelin (Svalbard) during a 11 year record. The daily temporal occurrence of NPF events likely caused by nucleation in the polar marine boundary layer was quantified annually as 18%, with a peak of 51% during summer months. Air mass trajectory analysis and atmospheric nitrogen and sulphur tracers link these frequent nucleation events to biogenic precursors released by open water and melting sea ice regions. The occurrence of such events across a full decade was anti-correlated with sea ice extent. New particles originating from open water and open pack ice increased the cloud condensation nuclei concentration background by at least ca. 20%, supporting a marine biosphere-climate link through sea ice melt and low altitude clouds that may have contributed to accelerate Arctic warming. Our results prompt a better representation of biogenic aerosol sources in Arctic climate models.

The structural basis of alpha-tropomyosin linked (Asp230Asn) familial dilated cardiomyopathy.

Recently, linkage analysis of two large unrelated multigenerational families identified a novel dilated cardiomyopathy (DCM)-linked mutation in the gene coding for alpha-tropomyosin (TPM1) resulting in the substitution of an aspartic acid for an asparagine (at residue 230). To determine how a single amino acid mutation in α-tropomyosin (Tm) can lead to a highly penetrant DCM we generated a novel transgenic mouse model carrying the D230N mutation. The resultant mouse model strongly phenocopied the early onset of cardiomyopathic remodeling observed in patients as significant systolic dysfunction was observed by 2months of age. To determine the precise cellular mechanism(s) leading to the observed cardiac pathology we examined the effect of the mutation on Ca2+ handling in isolated myocytes and myofilament activation in vitro. D230N-Tm filaments exhibited a reduced Ca2+ sensitivity of sliding velocity. This decrease in sensitivity was coupled to increase in the peak amplitude of Ca2+ transients. While significant, and consistent with other DCMs, these measurements are comprised of complex inputs and did not provide sufficient experimental resolution. We then assessed the primary structural effects of D230N-Tm. Measurements of the thermal unfolding of D230N-Tm vs WT-Tm revealed an increase in stability primarily affecting the C-terminus of the Tm coiled-coil. We conclude that the D230N-Tm mutation induces a decrease in flexibility of the C-terminus via propagation through the helical structure of the protein, thus decreasing the flexibility of the Tm overlap and impairing its ability to regulate contraction. Understanding this unique structural mechanism could provide novel targets for eventual therapeutic interventions in patients with Tm-linked cardiomyopathies.

Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment.

This corrects the article DOI: 10.1038/mp.2016.204.

Elevated CYP2C19 expression is associated with depressive symptoms and hippocampal homeostasis impairment.

The polymorphic CYP2C19 enzyme metabolizes psychoactive compounds and is expressed in the adult liver and fetal brain. Previously, we demonstrated that the absence of CYP2C19 is associated with lower levels of depressive symptoms in 1472 Swedes. Conversely, transgenic mice carrying the human CYP2C19 gene (2C19TG) have shown an anxious phenotype and decrease in hippocampal volume and adult neurogenesis. The aims of this study were to: (1) examine whether the 2C19TG findings could be translated to humans, (2) evaluate the usefulness of the 2C19TG strain as a tool for preclinical screening of new antidepressants and (3) provide an insight into the molecular underpinnings of the 2C19TG phenotype. In humans, we found that the absence of CYP2C19 was associated with a bilateral hippocampal volume increase in two independent healthy cohorts (N=386 and 1032) and a lower prevalence of major depressive disorder and depression severity in African-Americans (N=3848). Moreover, genetically determined high CYP2C19 enzymatic capacity was associated with higher suicidality in depressed suicide attempters (N=209). 2C19TG mice showed high stress sensitivity, impaired hippocampal Bdnf homeostasis in stress, and more despair-like behavior in the forced swim test (FST). After the treatment with citalopram and 5-HT1A receptor agonist 8OH-DPAT, the reduction in immobility time in the FST was more pronounced in 2C19TG mice compared with WTs. Conversely, in the 2C19TG hippocampus, metabolic turnover of serotonin was reduced, whereas ERK1/2 and GSK3ß phosphorylation was increased. Altogether, this study indicates that elevated CYP2C19 expression is associated with depressive symptoms, reduced hippocampal volume and impairment of hippocampal serotonin and BDNF homeostasis.

Cardiovascular risk factors and TIA characteristics in 19,872 Swedish TIA patients.

BACKGROUND: Transient ischemic attack (TIA) constitutes a major risk factor for stroke, making TIA patients an important group for secondary intervention. The aim of this study was to account for risk factor prevalence in TIA patients and analyze the association between TIA characteristics and risk factors. METHODS: We included 20,871 TIA events in 19,872 patients who were registered in the Swedish Riksstroke registry during the years 2010 through 2012. Data from other Swedish registers were used for comparison. The following variables were analyzed: age, sex, diabetes mellitus, atrial fibrillation (AF), cigarette smoking, and antihypertensive treatment. RESULTS: Compared to the general population (based on data retrieved from Sweden's national public health survey 'Health on equal terms'), TIA patients more often had diabetes mellitus (prevalence ratio, PR = 2.3), AF without oral anticoagulants (OAC) (PR = 2.8), and AF on OAC (PR = 1.6). Blood pressure medication was less prevalent among TIA patients than in the general population (PR = 0.57). Increasing age was associated with longer attacks. CONCLUSIONS: The fact that diabetes mellitus, atrial fibrillation, and smoking are more common in TIA patients than in the general population suggests that these factors are risk factors for TIA, even if causal relations cannot be proven. The relation between increasing age and longer attacks possibly reflects an increased proportion of embolic TIAs, or impaired recovery ability. Our results also suggest a significant proportion of untreated hypertension cases in the population.

Nanoparticle oxygen delivery to the ischemic heart.

OBJECTIVE: Currently there are no medications that can be administered to help deliver more oxygen to the myocardial region experiencing abnormal perfusion. The purpose of this study was to look at the nanoparticle dodecafluoropentane in an emulsion as an oxygen carrier. Using nanoparticles as an oxygen carrier is advantageous because they are able to carry oxygen past blockages that are obstructing red blood cells (6-8 µm) due to their smaller size (250 nm). With the reintroduction of oxygen to the ischemic muscle tissue, a reduced infarct size should be seen. METHODS: Male C57BL/6J mice underwent left anterior descending artery (LAD) ligation using 8-0 monofilament nylon suture. Immediately after ligation of the LAD, the control group received a 200-µl intravenous injection of phosphate buffered saline (PBS). The treated group received a dose of 0.6 ml/kg of dodecafluoropentane diluted to a total volume of 200 µl in PBS. The mice were then allowed to recover from anesthesia and were sacrificed 24 hours after the time of ligation. After the mice were sacrificed, the heart was excised and placed at -20°C for 20 minutes. The heart was then sliced into 1-mm sections and stained with tetrazolium red to identify the infarcted area. The area of infarct and ventricle were then analyzed using ImageJ software. RESULTS: The average area of infarct in comparison to the ventricle for the control mice was 29.3±0.04% compared to 11.7±0.02% for the dodecafluoropentane-treated mice. CONCLUSION: The use of dodecafluoropentane in this murine model of myocardial infarction showed a 60% reduction in infarct size (p<0.01). The possibility of using nanoparticles to deliver oxygen to hypoxic tissues has interesting implications and justifies further study.

Methods for long-term 17ß-estradiol administration to mice.

Rodent models constitute a cornerstone in the elucidation of the effects and biological mechanisms of 17ß-estradiol. However, a thorough assessment of the methods for long-term administration of 17ß-estradiol to mice is lacking. The fact that 17ß-estradiol has been demonstrated to exert different effects depending on dose emphasizes the need for validated administration regimens. Therefore, 169 female C57BL/6 mice were ovariectomized and administered 17ß-estradiol using one of the two commonly used subcutaneous methods; slow-release pellets (0.18 mg, 60-day release pellets; 0.72 mg, 90-day release pellets) and silastic capsules (with/without convalescence period, silastic laboratory tubing, inner/outer diameter: 1.575/3.175 mm, filled with a 14 mm column of 36 µg 17ß-estradiol/mL sesame oil), or a novel peroral method (56 µg 17ß-estradiol/day/kg body weight in the hazelnut cream Nutella). Forty animals were used as ovariectomized and intact controls. Serum samples were obtained weekly for five weeks and 17ß-estradiol concentrations were measured using radioimmunoassay. The peroral method resulted in steady concentrations within--except on one occasion--the physiological range and the silastic capsules produced predominantly physiological concentrations, although exceeding the range by maximum a factor three during the first three weeks. The 0.18 mg pellet yielded initial concentrations an order of magnitude higher than the physiological range, which then decreased drastically, and the 0.72 mg pellet produced between 18 and 40 times higher concentrations than the physiological range during the entire experiment. The peroral method and silastic capsules described in this article constitute reliable modes of administration of 17ß-estradiol, superior to the widely used commercial pellets.

Low-grade infection complicating silastic dural substitute 32 years post-operatively.

BACKGROUND: A complication of a silastic dural substitute is described, which appeared after 32 years-by far the longest latency period reported in the literature. METHODS: Case report and literature review. RESULTS: In 1971, a 20-year old woman suffered from an acute subdural haematoma and a temporal cerebral contusion due to a motorbike accident. She underwent an operation with evacuation of these and the dura was mended with a silastic duraplasty. Thirty-two years later she deteriorated with increased memory problems and dysphasia. CT revealed an expanding haemorrhagic mass around the previous duraplasty, which demanded surgery with removal of the silastic dural implant and evacuation of the haemorrhagic mass. Although the haemorrhagic mass enveloped the silastic implant, a contribution of the acrylate flap cannot be ruled out. Bacteriological cultures revealed Acinetobacter spp. in the CSF. Adequate post-operative antibiotic treatment was administered. The patient slowly improved, but the complication represented a major setback in her long-term cognitive and communicative functions. CONCLUSIONS: This case widens the previously reported time-frame of late complications by 60%, from 20 to 32 years, and will hopefully serve to increase the awareness of late infections and haemorrhages induced by silastic dural implants, thereby improving diagnosis and treatment in future cases.

Ear acupuncture or local anaesthetics as pain relief during postpartum surgical repair: a randomised controlled trial.

OBJECTIVE: To evaluate two methods of pain relief during postpartum surgical repair in regard to effectiveness, wound healing and patient evaluation. DESIGN: A randomised controlled trial testing a pragmatic set-up of brief training of clinicians. SETTING: Delivery ward at a Danish district hospital with approximately 1600 annual deliveries. POPULATION: Primiparous women with a vaginal delivery at term who needed surgical repair of lacerations to the labia or the vagina, perineal lacerations of first or second degree or mediolateral episiotomies. METHODS: The trial was set up to evaluate the effect of a brief 2-hour hands-on training in the use of ear acupuncture. All midwives (n = 36) in the department had previous experience in using acupuncture for obstetric pain relief. Pain and wound healing were evaluated using validated scores. Data collection was performed by research assistants blinded towards treatment allocation. Randomisation was computer assisted. A total of 207 women were randomised to receive ear acupuncture (105) and local anaesthetics (102), respectively. MAIN OUTCOME MEASURES: The primary outcome was pain during surgical repair. Secondary outcomes were wound healing at 24-48 hours and 14 days postpartum, participant satisfaction, revision of wound or dyspareunia reported 6 months postpartum. RESULTS: Pain during surgical repair was more frequently reported by participants allocated to ear acupuncture compared with participants receiving local anaesthetics (89 versus 54%, P < 0.01). Pain intensity during surgical repair was also reported higher (Visual Analogue Scale score 3.5 versus 1.5, P < 0.01). The ear acupuncture group received more additional pain relief during repair (53 versus 19%, P < 0.01). No difference was observed in wound healing at 24-48 hours or 14 days postpartum. Revision of wounds was rare, and no difference occurred in this trial. Comparable proportions of participants reported dyspareunia at 6 months. Patient satisfaction with the allocated pain-relief method was lower in the ear acupuncture group (69 versus 91%, P < 0.01) and fewer women would recommend the method to a friend (74 versus 91%, P < 0.01). CONCLUSIONS: Ear acupuncture as used in this trial was less effective for pain relief compared with a local anaesthetic. No difference was observed in wound healing, need for revision of wound or dyspareunia. Patient satisfaction with allocated pain-relief method was lower in the ear acupuncture group.

Enhanced transdermal delivery of low molecular weight heparin by barrier perturbation.

The purpose of this work was to investigate the in vitro transdermal delivery of low molecular weight heparin (LMWH). Hairless rat skin was mounted on Franz diffusion cells and treated with various enhancement strategies. Passive flux was essentially zero and remained low even after iontophoresis (0.065 U cm(-2) h(-1)) or application of ultrasound (0.058 U cm(-2) h(-1)). A significant increase in flux across tape stripped skin (4.0 U cm(-2) h(-1)) suggests the interaction of stratum corneum (SC) with LMWH which was confirmed using Differential Scanning Calorimetry and Fourier Transform-Infrared spectrophotometry. Maltose microneedles were then employed as a means to locally disrupt and bypass the SC. Transepidermal water loss (TEWL) and transcutaneous electrical resistance (TER) were measured to confirm the barrier disruption. Microneedles breached the SC resulting in increased TEWL, decreased TER and enhanced LMWH permeability (0.175 U cm(-2) h(-1)). Microneedles when used in conjunction with iontophoresis had a synergistic effect on LMWH delivery resulting in enhancement of flux by 14.7-fold as compared to iontophoresis used alone. Confocal laser scanning microscopy substantiated the evidence about LMWH interaction with SC. In conclusion, LMWH was shown to interact with SC and therefore tape stripping or microneedles dramatically increased its delivery due to disruption of the SC skin barrier.

Enhancement of transdermal delivery of heparin by various physical and chemical enhancement techniques.

Conventional anticoagulants such as unfractionated heparin and warfarin have numerous limitations compared with low-molecular-weight heparin (LMWH). However, the need for repetitive parenteral administration is still a major disadvantage of LMWH, and the absorption of macromolecules such as LMWH across the gastrointestinal tract is very poor. Due to these problems with oral delivery of LMWH, transdermal delivery can be considered as an alternate route of administration. However, overcoming the skin barrier is necessary for the transport of larger molecules across the stratum corneum. This review focuses on the transdermal delivery of LMWH, providing a brief overview of heparin delivery via invasive and oral routes and discusses the advantages of using LMWH rather than heparin for transdermal delivery, and the primary reasons for poor permeability of LMWH. Various strategies employed for transdermal delivery of heparin are summarized, and chemical and physical enhancement techniques or suitable formulations that can be used to improve transcutaneous penetration and various chemical enhancers that act on the skin by different modes of action are discussed. We also consider physical approaches such as iontophoresis, electroporation, and ultrasound, as well as combination strategies to deliver heparin. The developments in physical and chemical enhancement strategies over the past decade are summarized. In addition, recent novel approaches such as microneedles employed for the transdermal delivery of LMWH are also discussed.

Cinacalcet HCI (Sensipar/Mimpara) is an effective chronic therapy for hemodialysis patients with secondary hyperparathyroidism.

AIMS: This 1-year double-blind, placebo-controlled, multicenter study evaluated the long-term safety and efficacy of cinacalcet for the treatment of secondary hyperparathyroidism in patients receiving hemodialysis. METHOD: Patients were randomly assigned in a 1:1 ratio to cinacalcet or control treatment groups. The initial dose of cinacalcet (or matching placebo) was 30 mg. Doses were titrated every 3 or 4 weeks based on the intact parathyroid hormone (iPTH) response and safety profile. Sequential doses included 30, 60, 90, 120 and 180 mg/d. Phosphate binders and vitamin D sterols were adjusted per protocol as needed to control levels of calcium and phosphorus. Efficacy and safety were compared between treatment groups among patients who completed the study (52 total weeks of treatment). Reasons for withdrawal are presented for patients who did not complete the study. RESULTS: A total of 210 patients completed 52 weeks of double-blinded treatment with cinacalcet (n = 99) or placebo (n = 111). Over the last 6 months of the study, a greater proportion of patients in the cinacalcet group than the control group achieved an iPTH level < or = 250 pg/ml (61.6 vs. 9.9%, p < 0.001) or a > or = 30% decrease in iPTH from baseline (81.8 vs. 21.6%, p < 0.001). Mean iPTH levels decreased by -47.8% in the cinacalcet group and increased by +12.9% in the control group. Mean percentage changes in other laboratory values in the cinacalcet and control groups included the following: serum calcium -6.5 vs. +0.9% (p < 0.001), serum phosphorus -3.6 vs. -1.1% (p = 0.465), and Ca x P -9.9 vs. -0.3% (p = 0.006). The most commonly reported adverse events related to study drug by the investigators included nausea (13% cinacalcet, 5% control), investigator-reported hypocalcemia (11% cinacalcet, 1% control), vomiting (9% cinacalcet, 2% control), dyspepsia (5% cinacalcet, 4% control), and diarrhea (5% cinacalcet, 2% control). CONCLUSIONS: Treatment with cinacalcet is a safe and effective therapy for long-term control of secondary hyperparathyroidism. 1-year therapy with cinacalcet was associated with sustained, clinically significant reductions in calcium, Ca x P and iPTH which allowed a greater percentage of patients to achieve NKF-KDOQI target goals for PTH and Ca x P.

High natural aerosol loading over boreal forests.

Aerosols play a key role in the radiation balance of the atmosphere. Here, we present evidence that the European boreal region is a substantial source of both aerosol mass and aerosol number. The investigation supplies a straightforward relation between emissions of monoterpenes and gas-to-particle formation over regions substantially lacking in anthropogenic aerosol sources. Our results show that the forest provides an aerosol population of 1000 to 2000 particles of climatically active sizes per cubic centimeter during the late spring to early fall period. This has important implications for radiation budget estimates and relevancy for the evaluation of feedback loops believed to determine our future climate.

Heart failure in Parkinson's disease: analysis of the United States medicare current beneficiary survey.

OBJECTIVE: We sought to examine the prevalence of heart failure in elderly PD versus non-PD patients using a national sample of Medicare beneficiaries in the United States. SCOPE: The prevalence of heart failure in elderly PD patients was 2.27 times that of non-PD patients (19.4% versus 8.7%, 95% CI = 1.43-3.60, p 0.0005), and remained twice as high after excluding patients with stroke and possible vascular parkinsonism. CONCLUSIONS: In this cross-sectional study of a national Medicare database, heart failure occurred twice as frequently in elderly PD patients as in non-PD patients. Prospective studies are warranted to verify these findings.

Pharmacokinetics in Healthy Volunteers of Sumatriptan 25-mg Oral Tablet Versus 25-mg Extemporaneous Suppository.

The pharmacokinetics of an extemporaneous 25-mg suppository formulation of sumatriptan were compared to those of the marketed 25-mg oral tablet. Sixteen healthy volunteers enrolled in this open-label, two-way crossover study. Fifteen subjects completed the study. The pharmacokinetics of the suppository and the oral tablet were significantly different. Tmax was observed at 0.5 hours in 12 of 15 subjects with the extemporaneous suppository, compared with the range of 0.75 hours to 1.5 hours in 13 of 15 subjects with the oral tablet. The mean Cmax and area under the plasma concentration time curve were 5.4-fold and fourfold greater for the suppository than for the oral tablet. Both formulations were well tolerated, with mild headache experienced in only three subjects. Based upon its pharmacokinetic profile, the extemporaneous suppository may represent a useful alternative therapeutic administartion route for some patients.

One-year study of felodipine or placebo for stage 1 isolated systolic hypertension.

Asubstantial number of older hypertensive patients have stage 1 isolated systolic hypertension (systolic blood pressure between 140 and 159 mm Hg and diastolic blood pressure <90 mm Hg), but there are currently no data showing that drug treatment is effective, safe, and/or beneficial. To compare the effects of active treatment compared with placebo on blood pressure, left ventricular hypertrophy, and quality of life among older stage 1 isolated systolic hypertensive patients, a randomized, double-blind, parallel-group, multicenter clinical trial comparing felodipine (2.5, 5, or 10 mg once daily) and matching placebo was performed in 171 patients (49% male, average age 66+/-7 years, with 49% white and 30% Hispanic) with a baseline blood pressure of 149+/-7/83+/-6 mm Hg. During 52 weeks of treatment, patients randomized to active treatment achieved significantly lower blood pressures (137.0+/-11.7/80.2+/-7.6 mm Hg for extended-release felodipine versus 147.5+/-16.0/83.5+/-9.7 mm Hg for placebo, P<0.01 for each), a reduced incidence of left ventricular hypertrophy (7% for extended release felodipine versus 24% for placebo, P<0.04), and improved quality of life (change in Psychological General Well-Being index, 3.0+/-6.8 for extended-release felodipine versus -0.8+/-10.3 for placebo, P<0.01) versus baseline. There were no clinically significant differences between treatments in tolerability or adverse effects. Stage 1 isolated systolic hypertension can be effectively and safely treated pharmacologically. Treatment reduced progression to the higher stages of hypertension, reduced the incidence of left ventricular hypertrophy, and improved an overall measure of the quality of life. Larger and longer studies will be needed to document any long-term reduction in cardiovascular event rates associated with treating stage 1 systolic hypertension.

Jet eccentricity: a misleading source of agreement between Doppler/catheter pressure gradients in aortic stenosis.

Characterization of the severity of aortic stenosis relies on accurate measurement of the pressure gradient across the valve and the valve area. Pressure gradients measured by Doppler ultrasound based on the clinical form of the Bernoulli equation often overestimate pressure gradients by catheter as the result of pressure recovery. Doppler techniques measure the velocity of the vena contracta of the stenotic jet. This corresponds to the maximal pressure gradient and the minimal effective valve area. Pressure recovery can be characterized by analysis of the spread of the stenotic jet downstream of the valve as it fills the aorta and should be influenced by the shape of the velocity profile of the decaying jet. In this study, we addressed the hypothesis that the site of complete pressure recovery (the point at which the jet fully expands to the size of the aorta), the effective valve area, and the maximal pressure gradient are affected by jet eccentricity. To accomplish this, we developed a computational model of aortic stenosis that provides detailed velocity and pressure information in the vicinity of the valve. The results show that the width of the eccentric wall jet decreased and maximal velocity increased with greater jet eccentricity. Furthermore, for a constant anatomic area, the effective valve area decreased, the distance to complete pressure recovery increased, and the maximal pressure gradient increased with the degree of eccentricity. Failure to take this into account could fortuitously drive Doppler and catheter measurements toward agreement because the distal pressure sensor will not record the fully recovered pressure. Therefore the pressure gradient across a stenotic valve depends on jet eccentricity. The spread of the wall jet after attachment must be characterized to develop a robust method for the prediction of pressure recovery.