Elevated ferritin, mediated by IL-18 is associated with systemic inflammation and mortality in acute respiratory distress syndrome (ARDS).

BACKGROUND: Inflammatory subphenotypes have been identified in acute respiratory distress syndrome (ARDS). Hyperferritinaemia in sepsis is associated with hyperinflammation, worse clinical outcomes, and may predict benefit with immunomodulation. Our aim was to determine if raised ferritin identified a subphenotype in patients with ARDS. METHODS: Baseline plasma ferritin concentrations were measured in patients with ARDS from two randomised controlled trials of simvastatin (Hydroxymethylglutaryl-CoA Reductase Inhibition with Simvastatin in Acute Lung Injury to Reduce Pulmonary Dysfunction-2 (HARP-2); discovery cohort, UK) and neuromuscular blockade (ROSE; validation cohort, USA). Results were analysed using a logistic regression model with restricted cubic splines, to determine the ferritin threshold associated with 28-day mortality. RESULTS: Ferritin was measured in 511 patients from HARP-2 (95% of patients enrolled) and 847 patients (84% of patients enrolled) from ROSE. Ferritin was consistently associated with 28-day mortality in both studies and following a meta-analysis, a log-fold increase in ferritin was associated with an OR 1.71 (95% CI 1.01 to 2.90) for 28-day mortality. Patients with ferritin >1380 ng/mL (HARP-2 28%, ROSE 24%) had a significantly higher 28-day mortality and fewer ventilator-free days in both studies. Mediation analysis, including confounders (acute physiology and chronic health evaluation-II score and ARDS aetiology) demonstrated a statistically significant contribution of interleukin (IL)-18 as an intermediate pathway between ferritin and mortality. CONCLUSIONS: Ferritin is a clinically useful biomarker in ARDS and is associated with worse patient outcomes. These results provide support for prospective interventional trials of immunomodulatory agents targeting IL-18 in this hyperferritinaemic subgroup of patients with ARDS.

Sex-based differences in short- and longer-term diet-induced metabolic heart disease.

Sex-based differences in the development of obesity-induced cardiometabolic dysfunction are well documented, however, the specific mechanisms are not completely understood. Obesity has been linked to dysregulation of the epitranscriptome, but the role of N6-methyladenosine (m6A) RNA methylation has not been investigated in relation to the sex differences during obesity-induced cardiac dysfunction. In the current study, male and female C57BL/6J mice were subjected to short- and long-term high-fat/high-sucrose (HFHS) diet to induce obesogenic stress. Cardiac echocardiography showed males developed systolic and diastolic dysfunction after 4 mo of diet, but females maintained normal cardiac function despite both sexes being metabolically dysfunctional. Cardiac m6A machinery gene expression was differentially regulated by duration of HFHS diet in male, but not female mice, and left ventricular ejection fraction correlated with RNA machinery gene levels in a sex- and age-dependent manner. RNA-sequencing of cardiac transcriptome revealed that females, but not males may undergo protective cardiac remodeling early in the course of obesogenic stress. Taken together, our study demonstrates for the first time that cardiac RNA methylation machinery genes are regulated early during obesogenic stress in a sex-dependent manner and may play a role in the sex differences observed in cardiometabolic dysfunction.NEW & NOTEWORTHY Sex differences in obesity-associated cardiomyopathy are well documented but incompletely understood. We show for the first time that RNA methylation machinery genes may be regulated in response to obesogenic diet in a sex- and age-dependent manner and levels may correspond to cardiac systolic function. Our cardiac RNA-seq analysis suggests female, but not male mice may be protected from cardiac dysfunction by a protective cardiac remodeling response early during obesogenic stress.

Acute hypoxaemic respiratory failure after treatment with lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal: long-term outcomes from the REST randomised trial.

INTRODUCTION: Lower tidal volume ventilation, facilitated by veno-venous extracorporeal carbon dioxide removal (vv-ECCO2R), does not improve 90-day mortality in patients with acute hypoxaemic respiratory failure (AHRF). The aim of this analysis was to evaluate the effect of this therapeutic strategy on long-term outcomes. METHODS: This was a prespecified analysis of the REST trial, a UK-wide multicentre randomised clinical trial that compared lower tidal volume ventilation, facilitated by vv-ECCO2R (intervention), with standard care in the treatment of patients with moderate-to-severe AHRF. Mortality to 2 years was assessed, while respiratory function, post-traumatic stress disorder, cognitive function and health-related quality of life were evaluated in survivors at 1 year using standardised questionnaires. RESULTS: Of 412 patients enrolled into the REST trial, 391 (95%) had 2-year mortality outcome data available. There was no difference in the time to death between intervention and standard care (HR 1.08 (0.81, 1.44); log-rank test p=0.61). 161 patients alive at 1 year provided at least one questionnaire response. There was no difference in respiratory function, post-traumatic stress disorder, cognitive dysfunction or health-related quality of life between patients allocated to intervention or standard care. CONCLUSION: Lower-tidal volume ventilation facilitated by vv-ECCO2R does not affect 1-year mortality in patients with moderate-to-severe AHRF. Of the patients who provided questionnaire responses, there was no treatment effect on long-term respiratory function, post-traumatic stress disorder, cognitive dysfunction or health-related quality of life. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov identifier: NCT02654327.

Mind The Gap, Aboriginal and Torres Strait Islander Cardiovascular Health: A Narrative Review.

Australia's First Nations Peoples, Aboriginal and Torres Strait Islanders, have reduced life expectancy compared to the wider community. Cardiovascular diseases, mainly driven by ischaemic heart disease, are the leading contributors to this disparity. Despite over a third of First Nations Peoples living in New South Wales, the bulk of the peer-reviewed literature is from Central Australia and Far North Queensland. Regardless of the site of publication, First Nations Peoples are significantly younger at disease onset and have higher rates of comorbidities, in turn driving adverse health events. On top of this, very few First Nations Peoples specific cardiovascular interventions or programs have been shown to improve outcomes. The traditional biomedical model of care is less efficacious and non-traditional models of communication such as clinical yarning may benefit both clinicians and patients. The key purpose of this review is to highlight the deficiencies of our knowledge of cardiovascular burden of disease for First Nations Peoples; and to serve as a catalyst for more dedicated research. We need to have relationships with communities and concentrate on community improvement and partnerships. By involving First Nations Peoples researchers in collaboration with local communities in all levels of health care design and intervention will improve outcomes.

Natural history and prognostic implications of left ventricular end-diastolic pressure in reperfused ST-segment elevation myocardial infarction: an analysis of the thrombolysis in myocardial infarction (TIMI) II randomized controlled trial.

BACKGROUND: The aim of the current study is to assess the natural history and prognostic value of elevated left ventricular end-diastolic pressure (LVEDP) in patients with ST-segment elevation myocardial infarction (STEMI) after reperfusion with thrombolysis; we utilize data from the Thrombolysis in Myocardial Infarction (TIMI) II study. METHODS: A total of 3339 patients were randomized to either an invasive (n = 1681) or a conservative (n = 1658) strategy in the TIMI II study following thrombolysis. To make the current cohort as relevant as possible to modern pharmaco-invasively managed cohorts, patients in the invasive arm with TIMI flow grade ≥ 2 (N = 1201) at initial catheterization are included in the analysis. Of these, 259 patients had a second catheterization prior to hospital discharge, and these were used to define the natural history of LVEDP in reperfused STEMI. RESULTS: The median LVEDP for the whole cohort was 18 mmHg (IQR: 12-23). Patients were divided into quartiles by LVEDP measured during the first cardiac catheterization. During a median follow up of 3 (IQR: 2.1-3.2) years, quartile 4 (highest LVEDP) had the highest incidence of mortality and heart failure admissions. In the cohort with paired catheterization data, the LVEDP dropped slightly from 18 mmHg (1QR: 12-22) to 15 mmHg (IQR: 10-20) (p = 0.01) from the first to the pre-hospital discharge catheterization. CONCLUSIONS: LVEDP remains largely stable during hospitalisation post-STEMI. Elevated LVEDP is a predictor of death and heart failure hospitalization in STEMI patients undergoing successful thrombolysis.

Combined Mesenchymal Stromal Cell Therapy and Extracorporeal Membrane Oxygenation in Acute Respiratory Distress Syndrome. A Randomized Controlled Trial in Sheep.

Rationale: Mesenchymal stromal cell (MSC) therapy is a promising intervention for acute respiratory distress syndrome (ARDS), although trials to date have not investigated its use alongside extracorporeal membrane oxygenation (ECMO). Recent preclinical studies have suggested that combining these interventions may attenuate the efficacy of ECMO.Objectives: To determine the safety and efficacy of MSC therapy in a model of ARDS and ECMO.Methods: ARDS was induced in 14 sheep, after which they were established on venovenous ECMO. Subsequently, they received either endobronchial induced pluripotent stem cell-derived human MSCs (hMSCs) (n = 7) or cell-free carrier vehicle (vehicle control; n = 7). During ECMO, a low Vt ventilation strategy was employed in addition to protocolized hemodynamic support. Animals were monitored and supported for 24 hours. Lung tissue, bronchoalveolar fluid, and plasma were analyzed, in addition to continuous respiratory and hemodynamic monitoring.Measurements and Main Results: The administration of hMSCs did not improve oxygenation (PaO2/FiO2 mean difference = -146 mm Hg; P = 0.076) or pulmonary function. However, histological evidence of lung injury (lung injury score mean difference = -0.07; P = 0.04) and BAL IL-8 were reduced. In addition, hMSC-treated animals had a significantly lower cumulative requirement for vasopressor. Despite endobronchial administration, animals treated with hMSCs had a significant elevation in transmembrane oxygenator pressure gradients. This was accompanied by more pulmonary artery thromboses and adherent hMSCs found on explanted oxygenator fibers.Conclusions: Endobronchial hMSC therapy in an ovine model of ARDS and ECMO can impair membrane oxygenator function and does not improve oxygenation. These data do not recommend the safe use of hMSCs during venovenous ECMO.

Impact of fast-food outlet density on incidence of myocardial infarction in the Hunter region.

BACKGROUND: There is an established association between fast-food consumption and metabolic diseases. Some studies also suggest that calorie-dense food promotes a proinflammatory response, which is itself linked with myocardial infarction (MI). Whether increased fast-food availability is a risk factor for MI remains unknown. AIM: To investigate the role of fast-food outlet density (FFD) as a novel environmental risk factor for MI in the Hunter region, New South Wales (NSW). METHODS: We conducted a retrospective cohort study using a database of all MI events between 1996 and 2013, extracted from the Hunter Cardiac and Stroke Outcomes unit. FFD was calculated for each local government area (LGA) of the Hunter region, allowing for a comparative analysis. Stratification by fast-food outlet data and LGA resulted in a total of 3070 cases. Weighted linear regression was used to investigate the role of FFD on incidence of MI in regional and rural Australia. RESULTS: FFD was positively correlated with rates of MI, remaining consistent in both single and multivariate predictor models adjusting for age, obesity, hyperlipidaemia, hypertension, smoking status, diabetes and socioeconomic status (P < 0.001). An increase of one fast-food outlet corresponded with four additional cases of MI per 100 000 people per year (4.07, 95% confidence interval, 3.86-4.28). CONCLUSIONS: FFD was positively associated with incidence of MI in both rural and metropolitan areas of NSW. This relationship remained consistent after multivariate adjustment for standard cardiovascular risk factors, highlighting the importance of an individual's food environment as a potential contributor towards their health.

Hyperoxaemia and hypoxaemia are associated with harm in patients with ARDS.

BACKGROUND: Oxygen therapy is routinely administered to mechanically ventilated patients. However, there remains uncertainty about the optimal oxygen titration target in patients with the acute respiratory distress syndrome (ARDS). METHODS: Prospectively identified adult patients meeting the Berlin definition of ARDS between 1st January 2014 and 13th December 2016 were analyzed. Oxygen exposure variables were collected at 6-hourly intervals. The primary exposure was the average time-weighted partial pressure of arterial oxygen (PaO2) calculated over a maximum of 7 days from meeting ARDS criteria. The primary outcome was ICU mortality. Univariable and multivariable logistic regression analyses were performed to assess the impact of exposure variables on clinical outcomes. Results are presented as odds ratio [95% confidence interval]. RESULTS: 202 patients were included in the final analysis. Overall ICU mortality was 31%. The average time-weighted PaO2 during the first 7 days of ARDS was similar between non-survivors and survivors (11.3 kPa [10.2, 12.5] (84.8 mmHg [76.5, 93.8]) vs. 11.9 kPa [10.9, 12.6] (89.3 mmHg [81.8, 94.5]); p = 0.08). In univariable and multivariable analysis, average time-weighted PaO2 demonstrated a U-shaped relationship with ICU mortality. There was a similar relationship identified with hospital mortality. CONCLUSIONS: In patients with ARDS, the predicted probability of both ICU and hospital mortality was lowest when the average time-weighted PaO2 was between 12.5 and 14 kPa (93.8-105.0 mmHg), suggesting this is a reasonable oxygenation target for clinicians to aim for.

Effect of Lower Tidal Volume Ventilation Facilitated by Extracorporeal Carbon Dioxide Removal vs Standard Care Ventilation on 90-Day Mortality in Patients With Acute Hypoxemic Respiratory Failure: The REST Randomized Clinical Trial.

Importance: In patients who require mechanical ventilation for acute hypoxemic respiratory failure, further reduction in tidal volumes, compared with conventional low tidal volume ventilation, may improve outcomes. Objective: To determine whether lower tidal volume mechanical ventilation using extracorporeal carbon dioxide removal improves outcomes in patients with acute hypoxemic respiratory failure. Design, Setting, and Participants: This multicenter, randomized, allocation-concealed, open-label, pragmatic clinical trial enrolled 412 adult patients receiving mechanical ventilation for acute hypoxemic respiratory failure, of a planned sample size of 1120, between May 2016 and December 2019 from 51 intensive care units in the UK. Follow-up ended on March 11, 2020. Interventions: Participants were randomized to receive lower tidal volume ventilation facilitated by extracorporeal carbon dioxide removal for at least 48 hours (n = 202) or standard care with conventional low tidal volume ventilation (n = 210). Main Outcomes and Measures: The primary outcome was all-cause mortality 90 days after randomization. Prespecified secondary outcomes included ventilator-free days at day 28 and adverse event rates. Results: Among 412 patients who were randomized (mean age, 59 years; 143 [35%] women), 405 (98%) completed the trial. The trial was stopped early because of futility and feasibility following recommendations from the data monitoring and ethics committee. The 90-day mortality rate was 41.5% in the lower tidal volume ventilation with extracorporeal carbon dioxide removal group vs 39.5% in the standard care group (risk ratio, 1.05 [95% CI, 0.83-1.33]; difference, 2.0% [95% CI, -7.6% to 11.5%]; P = .68). There were significantly fewer mean ventilator-free days in the extracorporeal carbon dioxide removal group compared with the standard care group (7.1 [95% CI, 5.9-8.3] vs 9.2 [95% CI, 7.9-10.4] days; mean difference, -2.1 [95% CI, -3.8 to -0.3]; P = .02). Serious adverse events were reported for 62 patients (31%) in the extracorporeal carbon dioxide removal group and 18 (9%) in the standard care group, including intracranial hemorrhage in 9 patients (4.5%) vs 0 (0%) and bleeding at other sites in 6 (3.0%) vs 1 (0.5%) in the extracorporeal carbon dioxide removal group vs the control group. Overall, 21 patients experienced 22 serious adverse events related to the study device. Conclusions and Relevance: Among patients with acute hypoxemic respiratory failure, the use of extracorporeal carbon dioxide removal to facilitate lower tidal volume mechanical ventilation, compared with conventional low tidal volume mechanical ventilation, did not significantly reduce 90-day mortality. However, due to early termination, the study may have been underpowered to detect a clinically important difference. Trial Registration: ClinicalTrials.gov Identifier: NCT02654327.

Impact of Delay in Surgery on Outcome in Patients Undergoing Cardiac Revascularisation Surgery.

BACKGROUND: Diagnosis of critical coronary artery disease, including after acute coronary syndrome presentation (ACS), represents an important indication for early coronary artery bypass graft (CABG) surgery. The study aims to investigate the influence of time from diagnosis to CABG on outcomes and document barriers to early revascularisation. METHODS: All patients 18 years and older with an acute presentation due to ACS or critical coronary artery disease who were considered to require urgent inpatient cardiac surgery between January 2016-February 2019 were included in the study. The primary endpoints were 30-day all-cause mortality or readmission, 1-year all-cause mortality, all-cause readmission. The secondary endpoint was the rate of complications while waiting for surgery. The time duration between diagnostic coronary angiography and surgery was considered as the time interval. RESULTS: Of 266 eligible patients, 251 underwent surgical revascularisation with 15 (6%) not undergoing surgery due to preoperative complications (n=12) or due to perceived prohibitively high surgical risk (n=3). The majority (85%) were male (mean age 67 years), 37% of patients had diabetes and 71% had hypertension. Non-ST elevation myocardial infarction was documented in 51% of the patients. The median time between diagnosis and inpatient CABG was 7 days (IQR 5-11). Thirty-five per cent (35%) of patients experienced complications while awaiting surgery. Of the 266 patients, 140 patients (53% - cohort 1) underwent surgery within 7 days. The cohort 1 rate of complications was lower than in cohort 2 (surgery after 7 days) (24 vs 47%, p<0.001). Moreover, 1-year mortality was less in cohort 1 (2 vs 8%, p=0.029). CONCLUSION: In patients requiring urgent inpatient CABG, delay for more than 7 days is associated with a higher rate of in-hospital complications and worse 30 day and 12-month outcomes.

Contemporary trends in stroke complicating cardiac catheterisation.

BACKGROUND: Stroke remains an important complication of diagnostic cardiac catheterisation and percutaneous coronary intervention and is associated with high rates of in-hospital mortality. AIMS: To evaluate the incidence of stroke over a 10-year period and assess the long-term influence of stroke following cardiac catheterisation and PCI on functional outcomes, based on modified Rankin score and mortality. METHODS: The study was performed using a case-control design in a single tertiary referral centre. Patients were identified by correlating those patients undergoing cardiac catheterisation between October 2006 and December 2016 with patients who underwent neuroimaging within 7 days to identify possible cases of suspected stroke or transient ischaemic attack. RESULTS: A total of 21 510 patients underwent cardiac catheterisation during the study period. Sixty (0.28%) patients experienced stroke or transient ischaemic attack. Compared to control patients, those who did experience cerebral ischaemic events were older (70.5 vs 64 years; P < 0.001), with higher rates of atrial fibrillation, hypertension and diabetes mellitus. Stroke complicating cardiac catheterisation was associated with an increased risk of readmission, with a significantly higher hazard of readmission for stroke noted. Despite minimal functional impairment based on modified Rankin score, stroke was associated with a significant risk of early and cumulative mortality. Stroke incidence remained stable over the study period despite changes in procedural practice. CONCLUSIONS: The incidence and functional severity of stroke remains low despite evolving procedural practice with a stable incidence over time despite changes in procedural practice; however, post-procedural stroke confirms an increased mortality hazard.

Pre-hospital thrombolysis for ST-segment elevation myocardial infarction in regional Australia: long-term follow up.

BACKGROUND: Delivering reperfusion therapy to patients with ST-segment elevation myocardial infarction (STEMI) in regional areas without access to tertiary cardiology care remains challenging. The systems of care in Hunter New England Health, New South Wales, Australia (area covered = 130 000 km2 ) to provide reperfusion to patients with STEMI involve a 12-lead electrocardiogram in the ambulance, discussion between cardiologist and paramedic, followed by pre-hospital thrombolysis (PHT) delivered in ambulance to appropriate patients >60 min from the cardiac catheterisation laboratories. Patients who can access the cardiac catheterisation laboratories within 60 min are treated with primary percutaneous coronary intervention (PCI). AIMS: We have previously reported excellent 12-month outcomes for patients receiving PHT and the aim of the current analysis is to look at the long term outcomes. METHODS: We assessed long-term all-cause mortality and major adverse cardiovascular events of STEMI patients undergoing PHT in our health district from August 2008 to August 2013 and compared with the primary PCI group. RESULTS: One hundred and fifty (mean age: 62 ± 13 years, males: 76%, n = 114) patients were administered PHT and 334 patients (mean age: 65 ± 13 years, males: 75%, n = 251) underwent primary PCI during the study period. During a median follow up of 6.2 years (interquartile range: 4.8-7.4 years) all-cause mortality was 16% and 19% in the PHT and primary PCI groups respectively (P = 0.4). CONCLUSION: Our real-world experience shows that PHT followed by early transfer to a primary PCI-capable centre is an effective reperfusion strategy, with comparable results to primary PCI, and mortality benefits are sustained to more than 6 years.

Sedation and Analgesia for Cardiac Catheterisation and Coronary Intervention.

BACKGROUND: While cardiac catheterisation is typically well tolerated, discomfort and anxiety are commonplace. Sedation using anxiolytic and analgesic medications has the potential to ameliorate such symptoms, however, is variably employed, with lack of standardised regimens and limited evidence. METHODS: We performed a review of the role of sedation for cardiac catheterisation, including current practices and summarising available evidence relevant to diagnostic and interventional coronary procedures in the cardiac catheterisation laboratory. RESULTS: Use of sedation and the medication regimens employed are highly variable. Available relevant studies are limited in number and mostly small. Sedation appears to modestly reduce anxiety and pain in most studies. The incidence of radial spasm and the consequent need to alter access site is reduced with procedural sedation. The majority of existing evidence applies to benzodiazepines and opioid use, which appear acceptably efficacious and safe when used with appropriate training and staffing; noting opioid medications reduce the absorption of loading doses of oral anti-platelet drugs. CONCLUSIONS: In conclusion, benzodiazepines and opioids result a modest reduction in pain, improved patient tolerability and reduced risk of radial artery spasm. The decision on whether to use sedation, and which agent(s) and dose, should be individualised based on patient factors, including need for oral antiplatelet therapy administration. Appropriate staffing and monitoring is essential.

Device exchange versus nonexchange modalities in left ventricular assist device-specific infections: A systematic review and meta-analysis.

No standardized treatment algorithm exists for the management of continuous-flow left ventricular assist device (CF-LVAD)-specific infections. The aim of this systematic review and meta-analysis was to compare the outcomes of CF-LVAD-specific infections as managed by device exchange to other treatment modalities not involving device exchange. Electronic search was performed to identify all studies in the English literature relating to the management of CF-LVAD-specific infections. All identified articles were systematically assessed for selection criteria. Thirteen studies with 158 cases of CF-LVAD-specific infection were pooled for analysis. Overall, 18/158 (11.4%) patients underwent CF-LVAD exchange, and 140/158 (88.6%) patients were treated with non-exchange modalities. The proportion of patients with isolated driveline infections or pump or pocket infections did not differ significantly between the groups. During a mean follow-up of 290 days, there were no significant differences in the overall mortality [exchange 17.6% (4.3-50.6) vs. non-exchange 23.3% (15.8-32.9), P = 0.67] and infection recurrence rates [exchange 26.7% (8.7-58.0) vs. non-exchange 38.6% (15.4-68.5), P = 0.56]. In the setting of CF-LVAD-specific infections, device exchange does not appear to confer an advantage in the overall mortality and infection recurrence as compared to non-exchange modalities.

Hemocompatibility-Related Outcomes in the MOMENTUM 3 Trial at 6 Months: A Randomized Controlled Study of a Fully Magnetically Levitated Pump in Advanced Heart Failure.

BACKGROUND: The HeartMate 3 (HM3) Left Ventricular Assist System (LVAS) (Abbott) is a centrifugal, fully magnetically levitated, continuous-flow blood pump engineered to enhance hemocompatibility and reduce shear stress on blood components. The MOMENTUM 3 trial (Multicenter Study of MagLev Technology in Patients Undergoing Mechanical Circulatory Support Therapy With HeartMate 3) compares the HM3 LVAS with the HeartMate II (HMII) LVAS (Abbott) in advanced heart failure refractory to medical management, irrespective of therapeutic intention (bridge to transplant versus destination therapy). This investigation reported its primary outcome in the short-term cohort (n=294; 6-month follow-up), demonstrating superiority of the HM3 for the trial primary end point (survival free of a disabling stroke or reoperation to replace the pump for malfunction), driven by a reduced need for reoperations. The aim of this analysis was to evaluate the aggregate of hemocompatibility-related clinical adverse events (HRAEs) between the 2 LVAS. METHODS: We conducted a secondary end point evaluation of HRAE (survival free of any nonsurgical bleeding, thromboembolic event, pump thrombosis, or neurological event) in the short-term cohort (as-treated cohort n=289) at 6 months. The net burden of HRAE was also assessed by using a previously described hemocompatibility score, which uses 4 escalating tiers of hierarchal severity to derive a total score for events encountered during the entire follow-up experience for each patient. RESULTS: In 289 patients in the as-treated group (151 the HM3 and 138 the HMII), survival free of any HRAE was achieved in 69% of the HM3 group and in 55% of the HMII group (hazard ratio, 0.62; confidence interval, 0.42-0.91; P=0.012). Using the hemocompatibility score, the HM3 group demonstrated less pump thrombosis requiring reoperation (0 versus 36 points, P<0.001) or medically managed pump thrombosis (0 versus 5 points, P=0.02), and fewer nondisabling strokes (6 versus 24 points, P=0.026) than the control HMII LVAS. The net hemocompatibility score in the HM3 in comparison with the HMII patients was 101 (0.67±1.50 points/patient) versus 137 (0.99±1.79 points/patient) (odds ratio, 0.64; confidence interval, 0.39-1.03; P=0.065). CONCLUSIONS: In this secondary analysis of the MOMENTUM 3 trial, the HM3 LVAS demonstrated greater freedom from HRAEs in comparison with the HMII LVAS at 6 months. CLINICAL TRIAL REGISTRATION: URL: http://clinicaltrials.gov. Unique identifier: NCT02224755.

Identifying associations between diabetes and acute respiratory distress syndrome in patients with acute hypoxemic respiratory failure: an analysis of the LUNG SAFE database.

BACKGROUND: Diabetes mellitus is a common co-existing disease in the critically ill. Diabetes mellitus may reduce the risk of acute respiratory distress syndrome (ARDS), but data from previous studies are conflicting. The objective of this study was to evaluate associations between pre-existing diabetes mellitus and ARDS in critically ill patients with acute hypoxemic respiratory failure (AHRF). METHODS: An ancillary analysis of a global, multi-centre prospective observational study (LUNG SAFE) was undertaken. LUNG SAFE evaluated all patients admitted to an intensive care unit (ICU) over a 4-week period, that required mechanical ventilation and met AHRF criteria. Patients who had their AHRF fully explained by cardiac failure were excluded. Important clinical characteristics were included in a stepwise selection approach (forward and backward selection combined with a significance level of 0.05) to identify a set of independent variables associated with having ARDS at any time, developing ARDS (defined as ARDS occurring after day 2 from meeting AHRF criteria) and with hospital mortality. Furthermore, propensity score analysis was undertaken to account for the differences in baseline characteristics between patients with and without diabetes mellitus, and the association between diabetes mellitus and outcomes of interest was assessed on matched samples. RESULTS: Of the 4107 patients with AHRF included in this study, 3022 (73.6%) patients fulfilled ARDS criteria at admission or developed ARDS during their ICU stay. Diabetes mellitus was a pre-existing co-morbidity in 913 patients (22.2% of patients with AHRF). In multivariable analysis, there was no association between diabetes mellitus and having ARDS (OR 0.93 (0.78-1.11); p = 0.39), developing ARDS late (OR 0.79 (0.54-1.15); p = 0.22), or hospital mortality in patients with ARDS (1.15 (0.93-1.42); p = 0.19). In a matched sample of patients, there was no association between diabetes mellitus and outcomes of interest. CONCLUSIONS: In a large, global observational study of patients with AHRF, no association was found between diabetes mellitus and having ARDS, developing ARDS, or outcomes from ARDS. TRIAL REGISTRATION: NCT02010073 . Registered on 12 December 2013.

Mortality and Readmission Following Hospitalisation for Heart Failure in Australia: A Systematic Review and Meta-Analysis.

BACKGROUND: Heart failure (HF) is a common, costly condition with an increasing burden on Australian health care system resources. Knowledge of the burden of HF on patients and on the health system is important for resource allocation. This study is the first systematic review to estimate the mortality and readmission rates after hospitalisation for HF in the Australian population. METHODS: We searched for studies of HF hospitalisation in Australia published between January 1990 and May 2016, using a systematic search of PubMed, Medline, Scopus, Web of Science, EMBASE and Cochrane Library databases. Studies reporting 30-day and/or 1-year outcomes for mortality or readmission following hospitalisation were eligible and included in this study. RESULTS: Out of 2889 articles matching the initial search criteria, a total of 13 studies representing 67,255 patients were included in the final analysis. The pooled mean age of heart failure patients was 76.3 years and 51% were male (n=34,271). The pooled estimated 30-day and 1-year all-cause mortality were 8% and 25% respectively. The pooled estimated 30-day and 1-year all-cause readmission rates were 20% and 56% respectively. There is a high prevalence of comorbidities in heart failure patients. There were limited data on readmission and mortality in rural patients and Indigenous people. CONCLUSIONS: Heart failure hospitalisations in Australia are followed by substantial readmission and mortality rates.

Quantifying the Effects of Prior Acetyl-Salicylic Acid on Sepsis-Related Deaths: An Individual Patient Data Meta-Analysis Using Propensity Matching.

OBJECTIVE: The primary objective was to conduct a meta-analysis on published observational cohort data describing the association between acetyl-salicylic acid (aspirin) use prior to the onset of sepsis and mortality in hospitalized patients. STUDY SELECTION: Studies that reported mortality in patients on aspirin with sepsis with a comparison group of patients with sepsis not on prior aspirin therapy were included. DATA SOURCES: Fifteen studies described hospital-based cohorts (n = 17,065), whereas one was a large insurance-based database (n = 683,421). Individual-level patient data were incorporated from all selected studies. DATA EXTRACTION: Propensity analyses with 1:1 propensity score matching at the study level were performed, using the most consistently available covariates judged to be associated with aspirin. Meta-analyses were performed to estimate the pooled average treatment effect of aspirin on sepsis-related mortality. DATA SYNTHESIS: Use of aspirin was associated with a 7% (95% CI, 2-12%; p = 0.005) reduction in the risk of death as shown by meta-analysis with considerable statistical heterogeneity (I = 61.6%). CONCLUSIONS: These results are consistent with effects ranging from a 2% to 12% reduction in mortality risk in patients taking aspirin prior to sepsis onset. This association anticipates results of definitive studies of the use of low-dose aspirin as a strategy for reduction of deaths in patients with sepsis.

Heart Failure Hospitalisations in the Hunter New England Area Over 10 years. A Changing Trend.

BACKGROUND: Heart failure carries a major burden on our health system, mainly related to the high rate of hospital admission. An understanding of the recent trends in heart failure hospitalisation is essential to the future allocation of health resources. Our aim is to analyse the temporal trends in heart failure hospitalisation. METHODS: We extracted all separations in the Hunter New England Local Health District between 2005-2014 (n=40,119) with an ICD 10 code for heart failure (I-50) in the first four diagnoses on discharge. The numbers of hospitalisations were age-standardised to the 2001 Australian population and compared based on gender and remoteness. RESULTS: There was a decline in the age-standardised hospitalisation. However, there was a clear inflection point between 2009-2010, after which the decline levelled off. The absolute number of hospitalisations increased between 2010 and 2014. Heart failure hospitalisation was higher in males compared to females and rural compared to metropolitan inhabitants. CONCLUSION: The gains in heart failure treatment noted in recent years seem to have come to an end. Patients aged 75 years and older are contributing the majority of age-standardised hospitalisations.

Pre-hospital thrombolysis in ST-segment elevation myocardial infarction: a regional Australian experience.

OBJECTIVE: The system of care in the Hunter New England Local Health District for patients with ST-segment elevation myocardial infarction (STEMI) foresees pre-hospital thrombolysis (PHT) administered by paramedics to patients more than 60 minutes from the cardiac catheterisation laboratory (CCL), and primary percutaneous coronary intervention (PCI) at the CCL for others. We assessed the safety and effectiveness of the pre-hospital diagnosis strategy, which allocates patients to PHT or primary PCI according to travel time to the CCL. DESIGN, SETTING AND PARTICIPANTS: Prospective, non-randomised, consecutive, single-centre case series of STEMI patients diagnosed on the basis of a pre-hospital electrocardiogram (ECG), from August 2008 to August 2013. All patients were treated at the tertiary referral hospital (John Hunter Hospital, Newcastle). MAIN OUTCOME MEASURES: The primary efficacy endpoint was all-cause mortality at 12 months; the primary safety endpoint was bleeding. RESULTS: STEMI was diagnosed in 484 patients on the basis of pre-hospital ECG; 150 were administered PHT and 334 underwent primary PCI. The median time from first medical contact (FMC) to PHT was 35 minutes (IQR, 28-43 min) and to balloon inflation 130 minutes (IQR, 100-150 min). In the PHT group, 37 patients (27%) needed rescue PCI (median time, 4 h; IQR, 3-5 h). The 12-month all-cause mortality rate was 7.0% (PHT, 6.7%; PCI, 7.2%). The incidence of major bleeding (TIMI criteria) in the PHT group was 1.3%; no patients in the primary PCI group experienced major bleeding. CONCLUSION: PHT can be delivered safely by paramedical staff in regional and rural Australia with good clinical outcomes.