Coherent optical coupling to surface acoustic wave devices.

Surface acoustic waves (SAW) and associated devices are ideal for sensing, metrology, and hybrid quantum devices. While the advances demonstrated to date are largely based on electromechanical coupling, a robust and customizable coherent optical coupling would unlock mature and powerful cavity optomechanical control techniques and an efficient optical pathway for long-distance quantum links. Here we demonstrate direct and robust coherent optical coupling to Gaussian surface acoustic wave cavities with small mode volumes and high quality factors (>105 measured here) through a Brillouin-like optomechanical interaction. High-frequency SAW cavities designed with curved metallic acoustic reflectors deposited on crystalline substrates are efficiently optically accessed along piezo-active directions, as well as non-piezo-active (electromechanically inaccessible) directions. The precise optical technique uniquely enables controlled analysis of dissipation mechanisms as well as detailed transverse spatial mode spectroscopy. These advantages combined with simple fabrication, large power handling, and strong coupling to quantum systems make SAW optomechanical platforms particularly attractive for sensing, material science, and hybrid quantum systems.

Comparing left ventricular assist device inflow cannula angle between median sternotomy and thoracotomy using 3D reconstructions.

BACKGROUND: Left ventricular assist device (LVAD) implantation via thoracotomy has many potential advantages compared to conventional sternotomy, including improved inflow cannula (IFC) positioning. We compared the difference in IFC angles, postoperative, and long-term outcomes for patients with LVADs implanted via thoracotomy and sternotomy. METHODS: A single-center, retrospective analysis of 14 patients who underwent thoracotomy implantation was performed and matched with 28 patients who underwent sternotomy LVAD implantations for a total of 42 patients. Inclusion required a minimum LVAD support duration of 30 days and excluded concomitant procedures. A postoperative CT-chest was used to measure the angle the between the IFC and mitral valve in two-dimensions and results were compared with three-dimensional reconstruction using the same CT chest. Outcome data were extracted from medical records. RESULTS: There was no significant difference in gender, INTERMACS score, BMI, or age between the two groups. Median cardiopulmonary bypass time was longer in the thoracotomy group compared to the sternotomy group, 107 min (86-122) versus 76 min (56-93), p < 0.01. 3D reconstructions revealed less deviation of the IFC away from the mitral valve in devices implanted via thoracotomy compared to sternotomy, median (IQR) angle 16.3° (13.9°-21.0°) versus 23.2° (17.9°-26.4°), p < 0.01. Rates of pump thrombosis, stroke, and gastrointestinal bleeding were not significantly different. CONCLUSIONS: Devices implanted via thoracotomy demonstrated less deviation away from mitral valve. However, there was no difference in morbidity between the two approaches. 3D reconstruction of the heart is an innovative technique to measure angulation and is clinically advantageous when compared to 2D imaging.

Heart Transplantation From DCD Donors in Australia: Lessons Learned From the First 74 Cases.

Heart transplantation from donation after circulatory death (DCD) donors has the potential to substantially increase overall heart transplant activity. The aim of this report is to review the first 8 y of our clinical heart transplant program at St Vincent's Hospital Sydney, to describe how our program has evolved and to report the impact that changes to our retrieval protocols have had on posttransplant outcomes. Since 2014, we have performed 74 DCD heart transplants from DCD donors utilizing a direct procurement protocol followed by normothermic machine perfusion. Changes to our retrieval protocol have resulted in a higher retrieval rate from DCD donors and fewer rejections of DCD hearts during normothermic machine perfusion. Compared with our previously reported early experience in the first 23 transplants, we have observed a significant reduction in the incidence of severe primary graft dysfunction from 35% (8/23) to 8% (4/51) in the subsequent 51 transplant recipients ( P < 0.01). The only withdrawal time interval significantly associated with severe primary graft dysfunction was the asystolic warm ischemic time: 15 (12-17) versus 13 (11-14) min ( P < 0.05). One- and 5-y survival of DCD heart transplant recipients was 94% and 88%, comparable to that of a contemporary cohort of donation after brain death recipients: 87 and 81% ( P -value was not significant). In conclusion, heart transplantation from DCD donors has become a major contributor to our overall transplant activity accounting for almost 30% of all transplants performed by our program in the last 2 y, with similar DCD and donation after brain death outcomes.

Impact of frailty on mortality and morbidity in bridge to transplant recipients of contemporary durable mechanical circulatory support.

BACKGROUND: Frailty is associated with adverse outcomes in advanced heart failure. We studied the impact of frailty on postoperative outcomes in bridge to transplant (BTT) durable mechanical circulatory support (MCS) recipients. METHODS: Patients undergoing left ventricular assist device (LVAD, n = 96) or biventricular support (BiV, n = 11) as BTT underwent frailty assessment. Frailty was defined as ≥ 3 physical domains of the Fried's Frailty Phenotype (FFP) or ≥ 2 physical domains of the FFP plus cognitive impairment on the Montreal Cognitive Assessment (MoCA). RESULTS: No difference in mortality at 360 days was observed in frail (n = 6/38, 15.8%) vs non-frail (n = 4/58, 6.9%) LVAD supported patients, p = 0.19. However, there was a significant excess mortality in frail BiV (n = 4/5) vs non-frail BiV (n = 0/6) supported patients, p = 0.013. In all patients, frail patients compared to non-frail patients experienced longer intensive care unit stay, 12 vs 6 days (p < 0.0001) and hospital length of stay, 48 vs 27 days (p < 0.0001). There was no difference in hemocompatibility and infection related adverse events. The majority (n = 22/29, 75.9%) of frail patients became non-frail following MCS; contrastingly, a minority (n = 3/42, 7.1%) became frail from being non-frail (p = 0.0003). CONCLUSIONS: Abnormal markers of frailty are common in patients undergoing BTT-MCS support and those used herein predict mortality in BiV-supported patients, but not in LVAD patients. These findings may help us better identify patients who will benefit most from BiV-BTT therapy.

Anatomical human fitting of the BiVACOR total artificial heart.

BACKGROUND: BiVACOR is a novel total artificial heart (TAH) utilizing a single centrifugal magnetically levitated rotor with the ability to modulate pulsatile flow. The device has been successfully tested in a bovine model. We undertook a multicenter anatomical and virtual fitting study of the BiVACOR in patients undergoing heart transplantation. METHODS: 10 patients were recruited across two heart transplant centers. A sterilized 1:1 titanium model of the device was inserted into the patient's chest post heart explant, prior to implantation of the donor heart. Measurements were recorded in situ. The device was then removed. Following this, retrospective 3D reconstructions were created from computed tomography chest scans to simulate a virtual fitting. RESULTS: Mean age was 53 years (range 38-67). Mean BMI was 28 (range 20-37). Heart failure etiology was varied-with ischemic cardiomyopathy being the most common. Mean spine-to-sternum distance at the tenth thoracic vertebrae (T10) was 14 cm (range 11-18). Mean aorta to aortic Port distance was 0.2 cm (range 0-0.5). Mean pulmonary artery to pulmonary artery port distance was 4.2 cm (range 1-7). The device fitted suitably in all patients without gross distortion to the geometry between native vessel/chamber and port. CONCLUSIONS: This study described the anatomical and virtual fitting of the BiVACOR TAH. The device fit well within the chest cavities of all 10 patients, who represented a variety of body morphologies and heart failure etiology.

Power optimization for phase quantization with SOAs using the gain extinction ratio.

Phase-sensitive amplifiers (PSAs) can work as M - level phase quantizers when waves generated with specific phase values are allowed to mix coherently in a nonlinear medium. The quality of an M - level phase quantizer depends on the relative powers of the mixing waves and requires their optimization. If the mixing waves also experience gain in the nonlinear medium, such as in semiconductor optical amplifiers (SOAs), this optimization becomes non-trivial. In this paper, we present a general method to optimize phase quantization using a PSA made using an SOA, based on gain extinction ratio (GER), which is an experimentally measurable quantity. We present a simple theory to derive the optimal GER required to achieve an M -level quantization. We further experimentally demonstrate two- and four-level phase quantization schemes with an SOA, operated at the optimized GER, with pump power levels as low as 1 mW.

The impact of frailty on mortality after heart transplantation.

BACKGROUND: Frailty is prevalent in the patients with advanced heart failure; however, its impact on clinical outcomes after heart transplantation (HTx) is unclear. The aim of this study was to assess the impact of pre-transplant frailty on mortality and the duration of hospitalization after HTx. METHODS: We retrospectively reviewed the post-transplant outcomes of 140 patients with advanced heart failure who had undergone frailty assessment within the 6-month interval before HTx: 43 of them were frail (F) and 97 were non-frail (NF). RESULTS: Post-transplant survival rates for the NF cohort at 1 and 12 months were 97% (93-100) and 95% (91-99) (95% CI), respectively. In contrast, post-transplant survival rates for the F cohort at the same time points were 86% (76-96) and 74% (60-84) (p < 0.0008 vs NF cohort), respectively. The Cox proportional hazards regression analysis demonstrated that pre-transplant frailty was an independent predictor of post-transplant mortality with a hazard ratio of 3.8 (95% CI: 1.4-10.5). Intensive care unit and hospital length of stay were 2 and 7 days longer in the F cohort (both p < 0.05), respectively, than in the NF cohort. CONCLUSIONS: Frailty within 6 months before HTx is independently associated with increased mortality and prolonged hospitalization after transplantation. Future research should focus on the development of strategies to mitigate the adverse effects of pre-transplant frailty.

Cardiac donation after circulatory death.

PURPOSE OF REVIEW: Increasing number of patients with end-stage heart failure and those with improved survivorship from selective utilization of implantable mechanical circulatory support devices have added further burden and complexity to the transplant waitlist and on the rate-limiting availability of donor hearts from the standard pathway of donation after brain death. Unlike this conventional route, the increasing clinical use of donation after circulatory death (DCD) donor hearts necessitates a closer understanding of the logistics involved in the DCD process as well as of the risks associated with the unique pathophysiological consequences in this setting. RECENT FINDINGS: Notwithstanding a higher incidence of delayed graft function, the clinical utilization of DCD hearts for cardiac transplantation over the past five years has demonstrated this to be a well-tolerated and strategic alternative with excellent medium-term clinical outcomes. SUMMARY: The uptake of DCD heart transplantation remains selective and currently confined to Australia, the United Kingdom, Belgium, and more recently the USA. A more significant adoption will only come about through: a concerted effort to resolve the ethical and clinical controversies; a better understanding of postconditioning strategies; continued resolve to reduce the obligatory period of warm ischemia; and from better extracorporeal platforms that permit functional viability assessment of the DCD donor heart.

Outcomes of Donation After Circulatory Death Heart Transplantation in Australia.

BACKGROUND: Transplantation of hearts retrieved from donation after circulatory death (DCD) donors is an evolving clinical practice. OBJECTIVES: The purpose of this study is to provide an update on the authors' Australian clinical program and discuss lessons learned since performing the world's first series of distantly procured DCD heart transplants. METHODS: The authors report their experience of 23 DCD heart transplants from 45 DCD donor referrals since 2014. Donor details were collected using electronic donor records (Donate Life, Australia) and all recipient details were collected from clinical notes and electronic databases at St. Vincent's Hospital. RESULTS: Hearts were retrieved from 33 of 45 DCD donors. A total of 12 donors did not progress to circulatory arrest within the pre-specified timeframe. Eight hearts failed to meet viability criteria during normothermic machine perfusion, and 2 hearts were declined due to machine malfunction. A total of 23 hearts were transplanted between July 2014 and April 2018. All recipients had successful implantation, with mechanical circulatory support utilized in 9 cases. One case requiring extracorporeal membrane oxygenation subsequently died on the sixth post-operative day, representing a mortality of 4.4% over 4 years with a total follow-up period of 15,500 days for the entire cohort. All surviving recipients had normal cardiac function on echocardiogram and no evidence of acute rejection on discharge. All surviving patients remain in New York Heart Association functional class I with normal biventricular function. CONCLUSIONS: DCD heart transplant outcomes are excellent. Despite a higher requirement for mechanical circulatory support for delayed graft function, primarily in recipients with ventricular assist device support, overall survival and rejection episodes are comparable to outcomes from contemporary brain-dead donors.

Effects of extracorporeal membrane oxygenation pump flow, backflow cannulae, mean arterial blood pressure, and pulse pressure on Doppler-derived flow velocities of the lower limbs in patients on peripheral veno-arterial extracorporeal membrane oxygenation: A pilot study.

BACKGROUND: Reported rates of limb ischaemia on peripheral veno-arterial extracorporeal membrane oxygenation (pVA ECMO) vary from 1-52%. OBJECTIVES: Primary: To explore (i) the feasibility for appropriately trained intensive care unit staff to measure Doppler derived flow velocities of the lower limbs for patients on pVA ECMO; and (ii) whether these measurements are clinically useful. Secondary: explore the relationship between ECMO pump flow, backflow cannulae (BFC) properties, mean arterial blood pressure (MAP), and pulse pressure on flow velocities. METHOD: Inclusion criteria: age>18 years, on pVA ECMO >24 hours. EXCLUSION CRITERIA: any guardianship limitations and patients without a BFC. Serial patients receiving pVA-ECMO over a 10 month period had Doppler derived flow velocities of the lower limbs sampled. Simultaneously, other pertinent parameters were recorded. 80% inclusion was considered clinically feasible. Study personnel were asked for feedback regarding the ease and usefulness of studies. RESULTS: 15 of 17 patients were included: 88% inclusion. Mean peak systolic velocity (PSV) in the cannulated limb was 31 ± 29 cm/s in the dorsalis pedis (DP) and 27 ± 18 cm/s posterior tibial (PT). Similar flows were recorded in the non-cannulated limbs (DP 34 ± 29 cm/s, PT 44 ± 36 cm/s; P > 0.05). PSV was positively correlated with pulse pressure in cannulated and non-cannulated limbs respectively (r=0.63, P < 0.05; r=0.67 and P < 0.05). There was no significant correlation between PSV and MAP. ECMO pump flow and BFC were negatively correlated with PSV (r=-0.51, P < 0.05; r=-0.43, P < 0.05). CONCLUSION: It is generally feasible for ICU staff to measure flow velocities of the lower limbs for patients on pVA ECMO. It remains unclear how clinically useful these measurements are. Doppler derived flow velocities of arteries of the lower limbs of patients on pVA ECMO appear different to non-ECMO patients. PSV in the lower limbs of patients on pVA ECMO seems to be more related to pulse pressure than to other haemodynamic parameters.

56-year-old lady with transaortic gradient.

CLINICAL INTRODUCTION: A 56-year-old lady with a background of hypertension was admitted to our institution with acute pulmonary oedema. She reported gradual and increasingly severe dyspnoea on exertion over the preceding 12 months and, prior to presentation, her exercise tolerance was restricted to one flight of stairs. On transthoracic echocardiography during the index admission, left ventricular size and systolic function were normal, and peak and mean transaortic gradients were 67 mm Hg and 33 mm Hg, respectively, with a peak velocity of 3.9 m/s. No aortic incompetence or other significant valvular abnormality was noted. A transoesophageal echocardiogram was performed. Figure 1 depicts the mid-oesophageal parasternal long-axis view. What is the explanation behind the significant transaortic gradient?heartjnl;104/12/1036/F1F1F1Figure 1Transoesophageal echocardiogram, mid-oesophageal long-axis view at 135 degrees. QUESTION: What is the explanation behind the significant transaortic gradient?Ventricular septal defect Supravalvular aortic stenosisAortic valvular stenosisSubaortic membraneHypertrophic obstructive cardiomyopathy.

Learning to Individuate: The Specificity of Labels Differentially Impacts Infant Visual Attention.

This study examined differences in visual attention as a function of label learning from 6 to 9 months of age. Before and after 3 months of parent-directed storybook training with computer-generated novel objects, event-related potentials and visual fixations were recorded while infants viewed trained and untrained images (n = 23). Relative to a pretraining, a no-training control group (n = 11), and to infants trained with category-level labels (e.g., all labeled "Hitchel"), infants trained with individual-level labels (e.g., "Boris," "Jamar") displayed increased visual attention and neural differentiation of objects after training.

Pathophysiological Trends During Withdrawal of Life Support: Implications for Organ Donation After Circulatory Death.

BACKGROUND: Donation after circulatory death (DCD) provides an alternative pathway to deceased organ transplantation. Although clinical DCD lung, liver, and kidney transplantation are well established, transplantation of hearts retrieved from DCD donors has reached clinical translation only recently. Progress has been limited by concern regarding the viability of DCD hearts. The aim of this study was to document the pathophysiological changes that occur in the heart and circulation during withdrawal of life (WLS) support. METHODS: In a porcine asphyxia model, we characterized the hemodynamic, volumetric, metabolic, biochemical, and endocrine changes after WLS for up to 40 minutes. Times to circulatory arrest and electrical asystole were recorded. RESULTS: After WLS, there was rapid onset of profound hypoxemia resulting in acute pulmonary hypertension and right ventricular distension. Concurrently, progressive systemic hypotension occurred with a fall in left atrial pressure and little change in left ventricular volume. Mean times to circulatory arrest and electrical asystole were 8 ± 1 and 16 ± 2 minutes, respectively. Hemodynamic changes were accompanied by a rapid fall in pH, and rise in blood lactate, troponin-T, and potassium. Plasma noradrenaline and adrenaline levels rose rapidly with dramatic increases in coronary sinus levels indicative of myocardial release. CONCLUSIONS: These findings provide insight into the nature and tempo of the damaging events that occur in the heart and in particular the right ventricle during WLS, and give an indication of the limited timeframe for the implementation of potential postmortem interventions that could be applied to improve organ viability.

Improved heart function from older donors using pharmacologic conditioning strategies.

BACKGROUND: Hearts from older donors are increasingly being referred for transplantation. However, these hearts are more susceptible to ischemia-reperfusion injury (IRI), reflected in higher rates of primary graft dysfunction. We assessed a strategy of pharmacologic conditioning, supplementing Celsior (Genzyme, Naarden, The Netherlands) preservation solution with glyceryl trinitrate (GTN; Hospira Australia Pty, Ltd, Mulgrave, VIC, Australia), erythropoietin (EPO; Eprex; Janssen-Cilag, North Ryde, NSW, Australia), and zoniporide (ZON; Pfizer, Inc., Groton, CT), to protect older hearts against IRI and improve graft function. METHODS: Wistar rats, aged 3, 12, and 18 months old, were used to represent adolescent, 30-year-old, and 45-year-old human donors, respectively. Animals were subjected to brain death (BD) and hearts stored for 6 hours at 2° to 3°C in Celsior or Celsior supplemented with GTN+EPO+ZON. Cardiac function and lactate dehydrogenase before and after storage were assessed during ex vivo perfusion. Western blots and histopathology were also analyzed. RESULTS: After BD, 18-month hearts demonstrated impaired aortic flow, coronary flow, and cardiac output compared with 3-month hearts (p < 0.001 to p < 0.0001). After storage in Celsior, the recovery of aortic flow, coronary flow, and cardiac output in 18-month BD hearts was further impaired (p < 0.01 vs 3-month hearts). Percentage functional recovery of 18-month BD hearts stored in Celsior supplemented with GTN+EPO+ZON was equivalent to that of 3-month hearts and significantly improved compared with 18-month hearts stored in Celsior alone (p < 0.01 to p < 0.001), with reduced lactate dehydrogenase release (p < 0.01) and myocardial edema (p < 0.05) and elevated phosphorylated extracellular signal-related kinase 1/2 (p < 0.05) and phosphorylated Akt (p < 0.01). CONCLUSIONS: Older hearts are more susceptible to IRI induced by BD and prolonged hypothermic storage. Supplemented Celsior activates cell survival signaling in older hearts, reduces IRI, and enhances donor heart preservation.

Development of a Mock Extracorporeal Membrane Oxygenation Circuit to Assess Recirculation.

A limitation of veno-venous extracorporeal membrane oxygenation (VV-ECMO) is the recirculating of newly oxygenated blood back to the VV-ECMO circuit. We compared cannulation strategies for combating recirculation utilizing a mock circulation loop (MCL) with ultrasonic flow probes and pressure transducers ensuring that the MCL was run at physiological hemodynamic parameters. Mean recirculation percentages were lower (ANOVA, F = 14.25; p = 0.0001) with the Wang-Zwische dual lumen cannula (4.00 ± 1.77, n = 7) than both the femoro-jugular (15.23 ± 7.00, n = 8) and the femoro-femoral cannulation configurations (13.49 ± 1.44, n = 8).

Adult heart transplantation with distant procurement and ex-vivo preservation of donor hearts after circulatory death: a case series.

BACKGROUND: Orthotopic heart transplantation is the gold-standard long-term treatment for medically refractive end-stage heart failure. However, suitable cardiac donors are scarce. Although donation after circulatory death has been used for kidney, liver, and lung transplantation, it is not used for heart transplantation. We report a case series of heart transplantations from donors after circulatory death. METHODS: The recipients were patients at St Vincent's Hospital, Sydney, Australia. They received Maastricht category III controlled hearts donated after circulatory death from people younger than 40 years and with a maximum warm ischaemic time of 30 min. We retrieved four hearts through initial myocardial protection with supplemented cardioplegia and transferred to an Organ Care System (Transmedics) for preservation, resuscitation, and transportation to the recipient hospital. FINDINGS: Three recipients (two men, one woman; mean age 52 years) with low transpulmonary gradients (<8 mm Hg) and without previous cardiac surgery received the transplants. Donor heart warm ischaemic times were 28 min, 25 min, and 22 min, with ex-vivo Organ Care System perfusion times of 257 min, 260 min, and 245 min. Arteriovenous lactate values at the start of perfusion were 8·3-8·1 mmol/L for patient 1, 6·79-6·48 mmol/L for patient 2, and 7·6-7·4 mmol/L for patient 3. End of perfusion lactate values were 3·6-3·6 mmol/L, 2·8-2·3 mmol/L, and 2·69-2·54 mmol/L, respectively, showing favourable lactate uptake. Two patients needed temporary mechanical support. All three recipients had normal cardiac function within a week of transplantation and are making a good recovery at 176, 91, and 77 days after transplantation. INTERPRETATION: Strict limitations on donor eligibility, optimised myocardial protection, and use of a portable ex-vivo organ perfusion platform can enable successful, distantly procured orthotopic transplantation of hearts donated after circulatory death. FUNDING: NHMRC, John T Reid Charitable Trust, EVOS Trust Fund, Harry Windsor Trust Fund.

Gaze patterns of gross anatomy students change with classroom learning.

Numerous studies have documented that experts exhibit more efficient gaze patterns than those of less experienced individuals. In visual search tasks, experts use fewer, longer fixations to fixate for relatively longer on salient regions of the visual field while less experienced observers spend more time examining nonsalient regions. This study investigates whether changes in gaze patterns reflect learning by students in a medical gross anatomy course. Students were asked to examine photographs of dissections similar to those they experienced in class and to identify the tagged structure in each image. We postulated that, compared to naive behavior (behavior at baseline and when examining unfamiliar content) students would examine familiar content for longer and would direct proportionally more fixation time on cognitively salient regions of the images while using fewer, longer duration fixations. Our students examined familiar images for significantly longer than they did at baseline (P < 0.0001) or for unfamiliar images (P < 0.0001). They also spent significantly longer examining cognitively salient regions of familiar images, as compared to examining those regions at baseline (P < 0.0001) and on unfamiliar images (P < 0.0001). However, these gaze patterns were characterized by more numerous fixations rather than fewer, longer fixations. These individuals are successful learners in a challenging gross anatomy course, but are not experts in anatomy. Therefore we speculate that the gaze pattern they exhibit characterizes an earlier stage of the learning process than has previously been documented in studies of expertise, which have primarily focused on the gaze patterns of true experts.

Primary graft failure after heart transplantation.

Primary graft failure (PGF) is a devastating complication that occurs in the immediate postoperative period following heart transplantation. It manifests as severe ventricular dysfunction of the donor graft and carries significant mortality and morbidity. In the last decade, advances in pharmacological treatment and mechanical circulatory support have improved the outlook for heart transplant recipients who develop this complication. Despite these advances in treatment, PGF is still the leading cause of death in the first 30 days after transplantation. In today's climate of significant organ shortages and growing waiting lists, transplant units worldwide have increasingly utilised "marginal donors" to try and bridge the gap between "supply and demand." One of the costs of this strategy has been an increased incidence of PGF. As the threat of PGF increases, the challenges of predicting and preventing its occurrence, as well as the identification of more effective treatment modalities, are vital areas of active research and development.