Major adverse kidney events predict reduced survival in ventricular assist device supported patients.

AIMS: There is limited data describing major adverse kidney events (MAKE) in patients supported with ventricular assist devices (VAD). We aim to describe the association between MAKE and survival, risk factors for MAKE, and renal trajectory in VAD supported patients. METHODS AND RESULTS: We conducted a single-centre retrospective analysis of consecutive VAD implants between 2010 and 2019. Baseline demographics, biochemistry, and adverse events were collected for the duration of VAD support. MAKE was defined as the first event to occur of sustained drop (>50%) in estimated glomerular filtration rate (eGFR), progression to stage V chronic kidney disease, initiation or continuation of renal replacement therapy beyond implant admission or death on renal replacement therapy at any time. One-hundred and seventy-three patients were included, median age 56.8 years, 18.5% female, INTERMACS profile 1 or 2 in 75.1%. Thirty-seven patients experienced MAKE. On multivariate analysis, post-implant clinical right ventricular failure and the presence of chronic haemolysis, defined by the presence of schistocytes on blood film analysis, were significantly associated with increased risk of MAKE (adjusted odds ratio 9.88, P < 0.001 and adjusted odds ratio 3.33, P = 0.006, respectively). MAKE was associated with reduced survival (hazard ratio 4.80, P < 0.001). Patients who died or experienced MAKE did not demonstrate the expected transient 3-month improvement in eGFR, seen in other cohorts. CONCLUSIONS: MAKE significantly impacts survival. In our cohort, MAKE was predicted by post-implant right ventricular failure and chronic haemolysis. The lack of early eGFR improvement on VAD support may indicate higher risk for MAKE.

Extracorporeal Membrane Oxygenation for Graft Dysfunction Early After Heart Transplantation: A Systematic Review and Meta-analysis.

INTRODUCTION: Venoarterial extracorporeal membrane oxygenation (VA-ECMO) is a prevailing option for the management of severe early graft dysfunction. This systematic review and individual patient data (IPD) meta-analysis aims to evaluate (1) mortality, (2) rates of major complications, (3) prognostic factors, and (4) the effect of different VA-ECMO strategies on outcomes in adult heart transplant (HT) recipients supported with VA-ECMO. METHODS AND RESULTS: We conducted a systematic search and included studies of adults (≥18 years) who received VA-ECMO during their index hospitalization after HT and reported on mortality at any timepoint. We pooled data using random effects models. To identify prognostic factors, we analysed IPD using mixed effects logistic regression. We assessed the certainty in the evidence using the GRADE framework. We included 49 observational studies of 1477 patients who received VA-ECMO after HT, of which 15 studies provided IPD for 448 patients. There were no differences in mortality estimates between IPD and non-IPD studies. The short-term (30-day/in-hospital) mortality estimate was 33% (moderate certainty, 95% confidence interval [CI] 28%-39%) and 1-year mortality estimate 50% (moderate certainty, 95% CI 43%-57%). Recipient age (odds ratio 1.02, 95% CI 1.01-1.04) and prior sternotomy (OR 1.57, 95% CI 0.99-2.49) are associated with increased short-term mortality. There is low certainty evidence that early intraoperative cannulation and peripheral cannulation reduce the risk of short-term death. CONCLUSIONS: One-third of patients who receive VA-ECMO for early graft dysfunction do not survive 30 days or to hospital discharge, and one-half do not survive to 1 year after HT. Improving outcomes will require ongoing research focused on optimizing VA-ECMO strategies and care in the first year after HT.

Value of Renal Histology in Predicting Cardiorenal Outcomes in Heart Transplant-listed Patients.

Cardiorenal syndrome (CRS) contributes significantly to morbidity and mortality in patients requiring mechanical circulatory support and transplantation. There are no validated markers to predict major adverse kidney events (MAKEs), for which simultaneous heart-kidney transplant (SHKT) could offer improved survival. We evaluate renal histology in predicting MAKEs in transplant-listed patients. Methods: We identified 18 patients with renal histology consistent with CRS from 655 consecutive heart transplant-listed patients between 2010 and 2019. Biopsies were analyzed for glomerular, tubular, interstitial, and arteriolar changes tallied to give a biopsy chronicity score. The primary outcome, MAKE, was a composite of death, need for renal replacement therapy (RRT), or estimated glomerular filtration rate decline >50%. These were evaluated at 2 time points: before and following the transplant. Secondary outcomes included the individual components of the composite outcomes and the need for short-term RRT following the transplant. Results: The mean age was 52.3 y, 22% were female. Five patients did not survive to transplant. One patient underwent successful SHKT. MAKE occurred in 8 of 18 before the transplant and in 8 of 13 following the transplant. Neither outcome was predicted by baseline biochemistry. The biopsy chronicity score was significantly higher in patients with MAKE before transplant (4.3 versus 1.7, P = 0.024) and numerically higher in patients requiring short-term RRT following transplant (3.2 versus 0.7, P = 0.075). Contrary to limited previous literature, interstitial fibrosis did not predict any outcome, whereas tubular atrophy and arteriosclerosis were associated with MAKE before transplant. Conclusions: A higher biopsy chronicity score was associated with adverse kidney endpoints, raising its potential utility over standard biochemistry in considering SHKT referral.

Effects of Preoperative Angiotensin-Converting Enzyme Inhibitor Therapy on Postoperative Renal Function in Cardiac Surgery.

A Best Evidence Topic in cardiac surgery was written according to a structured protocol. The question addressed was-"In patients who undergo cardiac surgery, is preoperative angiotensin-converting enzyme inhibitor therapy associated with postoperative renal dysfunction?" Altogether, 339 papers were found using the reported search. Ten (10) were chosen which best answered the clinical question. The papers were evaluated for bias and heterogeneity using validated tools and the collected results analysed qualitatively. Evidence in the current literature is inconclusive that preoperative administration of angiotensin-converting enzyme inhibitor therapy affects postoperative renal dysfunction in patients undergoing cardiac surgery.

Vein Graft Patency Rates With Aspirin Plus Clopidogrel Following Coronary Artery Bypass Grafting.

A best evidence topic in cardiac surgery was written according to a structured protocol. The question addressed was, "In patients who have undergone Coronary Artery Bypass Grafting, does aspirin plus clopidogrel postoperatively improve vein graft patency when compared to aspirin alone?" Altogether, 165 papers were found using the reported search, of which five represented the best evidence to answer the clinical question. Overall analysis of these papers demonstrated similar rates of vein graft patency between the two groups. There was no difference between the groups with regard to mortality, adverse bleeding-related outcomes, or composite vascular events.

Drug-eluting versus bare-metal stents for saphenous vein graft lesions.

A best evidence topic was written addressing the question 'in patients with saphenous vein graft lesions requiring percutaneous coronary intervention, do long-term clinical outcomes differ between drug-eluting and bare-metal stents?' Altogether 1466 papers were found, of which seven represented the best evidence. Although one major recent randomised trial was neutral, the weight of earlier evidence supports drug-eluting stents as standard of care. Bare-metal stents may represent a reasonable, efficacious, and less expensive alternative to drug-eluting stents in well selected patient groups.

Do patients with the centrifugal flow HeartMate 3 or HeartWare left ventricular assist device have better outcomes compared to those with axial flow HeartMate II?

A best evidence topic was written according to a structured protocol. The question addressed was 'Do patients with centrifugal flow HeartMate 3 (HM3) or HeartWare left ventricular assist device (HVAD) have better outcomes compared to those with the axial flow HeartMate II (HMII)?' Altogether 1791 papers were found using the reported search, of which 21 represented the best evidence to answer the clinical question. The authors, journal, date and country of publication, patient group studied, study type, relevant outcomes and results of these papers are tabulated. In publications reporting on MOMENTUM 3 randomized control trial (RCT), HM3 had better outcomes compared to HMII with a lower rate of pump thrombosis (1.1% vs 15.7%), stroke events (10.1% vs 19.2%) and ischaemic stroke (6.3% vs 13.4%) at 2-year follow-up. Markers of quality of life and functional capacity were comparable between the 2 devices at 6 months. In publications reporting on ENDURANCE RCTs, compared to HMII, patients with HVAD had poorer outcomes with an increased rate of sepsis (23.6% vs 15.4%), stroke (29.7% vs 12.1%) and right heart failure (38.5% vs 26.8%) postoperatively. Outcomes were improved for the HVAD group in a more recent RCT where strict blood pressure control was instigated postoperatively. Outcomes from retrospective studies comparing HMII with HVAD varied, with some publications reporting higher rates of right ventricular assist device use (29% vs 15%), gastrointestinal bleeding (30% vs 0%), cerebrovascular accident (44% vs 10%), transient ischaemic attack (5% vs 2%) and higher cumulative risk of infection and haemorrhagic cerebrovascular accident with HVAD. This is not consistent across these studies, and 9 studies including a systematic review reported no difference in any outcomes. In conclusion, patients with centrifugal flow HM3 have better outcomes than those with axial flow HMII. Although there is some variability in outcomes in retrospective studies, patients with centrifugal flow HeartWare HVAD have similar outcomes to those with axial flow HMII when strict blood pressure control is instigated postoperatively. By inference, centrifugal flow HM3 would appear to be the superior device, although all conclusions are based on 1 large (industry-sponsored) RCT.

Management of atrial fibrillation after cardiac surgery.

A best evidence topic in cardiac surgery was written according to a structured protocol addressing the question 'for post-cardiac surgery atrial fibrillation (AF), do clinical outcomes differ between rate or rhythm control strategies?' Altogether, 2174 papers were found using the reported searches, of which 5 represented the best evidence to answer the clinical question. Hospital length of stay ranged from 5.0 to 13.2 days for rate control and 5.2 to 10.3 days for rhythm control. Freedom from AF at follow up was achieved in 84.2-91 and 84.2-96% in rate and rhythm control groups respectively. Minimal serious adverse events were noted in all studies analysed and there was no difference between rate and rhythm control groups. We conclude that in the management of post-cardiac surgery, AF, rate control and rhythm control are equivalent in terms of hospital length of stay, freedom from arrhythmia at follow up and complication rates.

Plugging Paravalvular Leak in Transcatheter Aortic Valves.

Paravalvular leak can complicate transcatheter aortic valve replacement with important prognostic implications. Correction of defects requires complex planning and execution. Multiple or irregular lesions, calcified annulus, and high sealing skirts on self-expandable devices are especially challenging. Such defects may be approximated using malleable vascular closure devices. (Level of Difficulty: Intermediate.).

Levosimendan Following Cardiac Surgery.

A best evidence topic was written to address if perioperative levosimendan improves mortality following cardiac surgery. Fourteen papers represented the best available evidence. An older meta-analysis summarising 11 of these trials concluded that there were fewer deaths in the levosimendan group compared to the control group (OR 0.41, p <0.001) however, this was driven by the results of three included trials by the same author. Three larger and more recent randomised controlled trials failed to demonstrate significant differences in mortality. We conclude that levosimendan lacks robust evidence to substantiate claims of mortality benefit in cardiac surgery patients and should not be used routinely in such patients.

Peripheral Arterial Disease.

Peripheral arterial disease (PAD) affects 15% of the Australian population and is a powerful and serious predictor of cardiovascular mortality yet continues to be under-recognised and undertreated. Diagnosis is simple and management is centred upon symptom relief and risk minimisation. While novel and specialised therapies play a role, the bulk of management is approachable and feasible. In this review, we cover the epidemiology, risk factors, associated conditions, classification, and natural history of PAD. We then discuss current diagnostic and therapeutic options as well as emerging therapies for this common condition.

Single layer graphene as an electrochemical platform.

Over the past decade, there has been a great deal of interest in graphene with regards to its electrochemical behavior. Previous studies have focused on understanding fundamental processes such as charge transfer and molecular transport at the graphene-electrolyte interface as well as on applications of graphene in electronic, optical, and mechanical systems. We present illustrative examples of large area, single layer graphene platforms for applications such as optical and sensing devices as well as microfluidic systems. Three examples of graphene modified with thin polymer films are discussed. We have explored the use of graphene as an electrochemical platform for surface-generated electrogenerated chemiluminescence (ECL) using poly-[Ru(v-bpy)3](2+), where v-bpy is 4-vinyl, 4'-methyl 2,2'-bipyridine, as a model system. We found that while graphene can sustain ECL conditions, there was film degradation during ECL, as demonstrated by a decrease in ECL intensity upon potential cycling even in the presence of a graphene coating ("graphene blanket"). Using poly 3,4-ethylenedioxythiophene (EDOT), we demonstrate a facile method of fabricating electrochromic electrodes from large area graphene. The oxidation of NADH at graphene was catalyzed using an electrodeposited layer of 3,4-dihydroxybenzaldehyde as an effective redox mediator. In addition, we describe the fabrication and characterization of a microfluidic device based on a solution-gated field effect transistor which was able to detect changes of 60 mV per pH unit change in an inverted cell design. On the other hand, a 29 mV shift in the Dirac point per unit pH change was measured with our microfluidic devices, and a ca. 10% FET conductance change was measured when we continuously changed the pH in solution from 6.91 to 7.64 in the microfluidic channel, demonstrating local microfluidic pH sensing (albeit non-Nerstian) in real time.

Poly(2,5-dimercapto-1,3,4-thiadiazole) as a cathode for rechargeable lithium batteries with dramatically improved performance.

Organosulfur compounds with multiple thiol groups are promising for high gravimetric energy density electrochemical energy storage. We have synthesized a poly(2,5-dimercapto-1,3,4-thiadiazole) (PDMcT)/poly(3,4-ethylenedioxythiophene) (PEDOT) composite cathode for lithium-ion batteries with a new method and investigated its electrochemical behavior by charge/discharge cycles and cyclic voltammetry (CV) in an ether-based electrolyte. Based on a comparison of the electrochemical performance with a carbonate-based electrolyte, we found a much higher discharge capacity, but also a very attractive cycling performance of PDMcT by using a tetra(ethylene glycol) dimethyl ether (TEGDME)-based electrolyte. The first discharge capacity of the as-synthesized PDMcT/PEDOT composite approached 210 mAh g(-1) in the TEGDME-based electrolyte. CV results clearly show that the redox reactions of PDMcT are highly reversible in this TEGDME-based electrolyte. The reversible capacity remained around 120 mAh g(-1) after 20 charge/discharge cycles. With improved cycling performance and very low cost, PDMcT could become a very promising cathode material when combined with a TEGDME-based electrolyte. The poor capacity in the carbonate-based electrolyte is a consequence of the irreversible reaction of the DMcT monomer and dimer with the solvent, emphasizing the importance of electrolyte chemistry when studying molecular-based battery materials.

Dynamics in an idealized ionic liquid model.

An idealized four-site ionic liquid model having characteristics approximating those of 1-butyl-3-methylimidazolium hexafluorophosphate ([Im(41)][PF(6)]) is introduced as a low-cost alternative to existing all-atom models for purposes of simulating solute-based dynamics over nanosecond and longer time scales. The structural and energetic properties of the model are in reasonable agreement with those of [Im(41)][PF(6)] and similar ionic liquids, but the dynamics are unrealistically slow. A temperature shift of approximately 100 K is required to produce agreement between the viscosity and diffusion coefficients of the model and experimental values. Several aspects of the ion dynamics such as subdiffusive translational motions, non-Gaussian van Hove distributions, and jumplike displacements in both positions and orientations, are similar to behavior observed in supercooled liquids. Translational diffusion coefficients and rotational correlation times show roughly the proportionalities to viscosity expected from hydrodynamic models, and slip hydrodynamic calculations provide reasonable accuracy in some cases. But anomalously high rotational diffusion coefficients which decouple from viscosity at low temperature are also observed. These anomalies are explained in terms of the prevalence of 180 degrees rotational jumps coupled to the presence of marked heterogeneity in rotational motions, especially about one molecular axis. Comparisons between the dynamics observed in the ionic liquid (IL) model and a neutral mixture (NM) counterpart help to explain the origins of the distinctive dynamics in ionic liquids compared to conventional solvents. The requirement for balancing electrostatic interactions in the IL leads to uniform and interleaved distributions of cations and anions resembling a distorted ionic lattice, similar to the structure of molten NaCl. The resistance to reorganizing this structure is what leads to the slow dynamics of ionic liquids. The coupling among large collections of ions is presumably responsible for the similarity of ionic liquids to supercooled conventional liquids.