Clinical to Population Prevalence of Hypertrophic Cardiomyopathy Phenotype: Insights From the National Echo Database Australia.

BACKGROUND: There is a paucity of data describing the underlying prevalence of hypertrophic cardiomyopathy (HCM), a primary genetic disorder characterised by progressive left ventricular (LV) hypertrophy and sudden death, from both a clinical and a population perspective. METHODS: We screened the echocardiographic reports of 155,668 men and 147,880 women within the multicentre National Echo Database Australia (NEDA) (2001-2019). End-diastolic wall thickness ≥15 mm anywhere in the left ventricle was identified as a characteristic of an HCM phenotype according to current guideline recommendations. Applying a septal-to-posterior wall thickness ratio >1.3 and LV outflow tract obstruction ≥30 mmHg (when documented), we further identified asymmetric septal hypertrophy and obstructive HCM (oHCM), respectively. The observed pattern of phenotypical HCM within the overall NEDA cohort (>650,000 cases) was then extrapolated to the ∼539,000 (5.7% of adult population) and ∼474,000 (4.8%) Australian men and women, respectively, who were investigated with echocardiography in 2021 on an age-specific basis. RESULTS: Overall, 15,380 cases (mean age 71.1±14.6 years, 10,138 men [65.9%]) with the characteristic HCM phenotype within the NEDA cohort were identified. Of these 15,380 cases, 5,552 (36.1%) had asymmetric septal hypertrophy, and 2,276 of the 10,290 cases with LV outflow tract obstruction profiling data (22.1%) had obstructive HCM. A further 3,389 of 13,715 cases (24.7%) had evidence of LV systolic dysfunction (LV ejection fraction <55%). Within the entire NEDA cohort (including those without LV profiling), HCM was found in 10,138 of 342,161 men (2.96%; 95% confidence interval [CI] 2.91%-3.02%) and 5,242 of 308,539 women (1.70%; 95% CI 1.65%-1.75%). When extrapolated to the Australian population, we estimate that a minimum of 15,971 men and 8,057 women presented with echocardiographic features of phenotypical HCM in 2021. This translates into a minimum caseload/prevalence of ∼17 adult men (∼2.5 in those aged ≤50 years) and eight adult women (∼1 in those aged ≤50 years) per 10,000 population meeting phenotypical HCM criteria. CONCLUSIONS: Using contemporary Australian echocardiographic and population data, we estimate that a minimum of 15,971 (17.5 cases/10,000) men and 8,057 women (8.2 cases/10,000) had echocardiographic evidence of phenotypical HCM in 2021. These disease burden data are particularly relevant as new treatment options are emerging.

When are bacteria really gazelles? Comparing patchy ecologies with dimensionless numbers.

From micro to planetary scales, spatial heterogeneity-patchiness-is ubiquitous in ecosystems, defining the environments in which organisms move and interact. However, most large-scale models still use spatially averaged 'mean fields' to represent natural populations, while fine-scale spatially explicit models are mostly restricted to particular organisms or systems. In a conceptual paper, Grünbaum (2012, Interface Focus 2: 150-155) introduced a heuristic, based on three dimensionless ratios quantifying movement, reproduction and resource consumption, to characterise patchy ecological interactions and identify when mean-field assumptions are justifiable. We calculated these dimensionless numbers for 33 interactions between consumers and their resource patches in terrestrial, aquatic and aerial environments. Consumers ranged in size from bacteria to whales, and patches lasted from minutes to millennia, with separation scales from mm to hundreds of km. No interactions could be accurately represented by naive mean-field models, though 19 (58%) could be partially simplified by averaging out movement, reproductive or consumption dynamics. Clustering interactions by their non-dimensional ratios revealed several unexpected dynamic similarities. For example, bacterial Pseudoalteromonas exploit nutrient plumes similarly to Mongolian gazelles grazing on ephemeral steppe vegetation. We argue that dimensional analysis is valuable for characterising ecological patchiness and can link widely different systems into a single quantitative framework.

Blue Waters, Green Bottoms: Benthic Filamentous Algal Blooms Are an Emerging Threat to Clear Lakes Worldwide.

Nearshore (littoral) habitats of clear lakes with high water quality are increasingly experiencing unexplained proliferations of filamentous algae that grow on submerged surfaces. These filamentous algal blooms (FABs) are sometimes associated with nutrient pollution in groundwater, but complex changes in climate, nutrient transport, lake hydrodynamics, and food web structure may also facilitate this emerging threat to clear lakes. A coordinated effort among members of the public, managers, and scientists is needed to document the occurrence of FABs, to standardize methods for measuring their severity, to adapt existing data collection networks to include nearshore habitats, and to mitigate and reverse this profound structural change in lake ecosystems. Current models of lake eutrophication do not explain this littoral greening. However, a cohesive response to it is essential for protecting some of the world's most valued lakes and the flora, fauna, and ecosystem services they sustain.

Kidney age - chronological age difference (KCD) score provides an age-adapted measure of kidney function.

BACKGROUND: Given the age-related decline in glomerular filtration rate (GFR) in healthy individuals, we examined the association of all-cause death or cardiovascular event with the Kidney age - Chronological age Difference (KCD) score, whereby an individual's kidney age is estimated from their estimated GFR (eGFR) and the age-dependent eGFR decline reported for healthy living potential kidney donors. METHODS: We examined the association between death or cardiovascular event and KCD score, age-dependent stepped eGFR criteria (eGFRstep), and eGFR < 60 ml/min/1.73 m2 (eGFR60) in a community-based high cardiovascular risk cohort of 3837 individuals aged ≥60 (median 70, interquartile range 65, 75) years, followed for a median of 5.6 years. RESULTS: In proportional hazards analysis, KCD score ≥ 20 years (KCD20) was associated with increased risk of death or cardiovascular event in unadjusted analysis and after adjustment for age, sex and cardiovascular risk factors. Addition of KCD20, eGFRstep or eGFR60 to a cardiovascular risk factor model did not improve area under the curve for identification of individuals who experienced death or cardiovascular event in receiver operating characteristic curve analysis. However, addition of KCD20 or eGFR60, but not eGFRstep, to a cardiovascular risk factor model improved net reclassification and integrated discrimination. KCD20 identified individuals who experienced death or cardiovascular event with greater sensitivity than eGFRstep for all participants, and with greater sensitivity than eGFR60 for participants aged 60-69 years, with similar sensitivities for men and women. CONCLUSIONS: In this high cardiovascular risk cohort aged ≥60 years, the KCD score provided an age-adapted measure of kidney function that may assist patient education, and KCD20 provided an age-adapted criterion of eGFR-related increased risk of death or cardiovascular event. Further studies that include the full age spectrum are required to examine the optimal KCD score cut point that identifies increased risk of death or cardiovascular event, and kidney events, associated with impaired kidney function, and whether the optimal KCD score cut point is similar for men and women. TRIAL REGISTRATION: ClinicalTrials.gov NCT00400257 , NCT00604006 , and NCT01581827 .

Excess mortality at Christmas due to cardiovascular disease in the HUNT study prospective population-based cohort in Norway.

BACKGROUND: Although it is known that winter inclusive of the Christmas holiday period is associated with an increased risk of dying compared to other times of the year, very few studies have specifically examined this phenomenon within a population cohort subject to baseline profiling and prospective follow-up. In such a cohort, we sought to determine the specific characteristics of mortality occuring during the Christmas holidays. METHODS: Baseline profiling and outcome data were derived from a prospective population-based cohort with longitudinal follow-up in Central Norway - the Trøndelag Health (HUNT) Study. From 1984 to 1986, 88% of the target population comprising 39,273 men and 40,353 women aged 48 ± 18 and 50 ± 18 years, respectively, were profiled. We examined the long-term pattern of mortality to determine the number of excess (all-cause and cause-specific) deaths that occurred during winter overall and, more specifically, the Christmas holidays. RESULTS: During 33.5 (IQR 17.1-34.4) years follow-up, 19,879 (50.7%) men and 19,316 (49.3%) women died at age-adjusted rate of 5.3 and 4.6 deaths per 1000/annum, respectively. Overall, 1540 (95% CI 43-45 deaths/season) more all-cause deaths occurred in winter (December to February) versus summer (June to August), with 735 (95% CI 20-22 deaths per season) of these cardiovascular-related. December 25th-27th was the deadliest 3-day period of the year; being associated with 138 (95% CI 96-147) and 102 (95% CI 72-132) excess all-cause and cardiovascular-related deaths, respectively. Accordingly, compared to 1st-21st December (equivalent winter conditions), the incidence rate ratio of all-cause mortality increased to 1.22 (95% CI 1.16-1.27) and 1.17 (95% 1.11-1.22) in men and women, respectively, during the next 21 days (Christmas/New Year holidays). All observed differences were highly significant (P < 0.001). A less pronounced pattern of mortality due to respiratory illnesses (but not cancer) was also observed. CONCLUSION: Beyond a broader pattern of seasonally-linked mortality characterised by excess winter deaths, the deadliest time of year in Central Norway coincides with the Christmas holidays. During this time, the pattern and frequency of cardiovascular-related mortality changes markedly; contrasting with a more stable pattern of cancer-related mortality. Pending confirmation in other populations and climates, further research to determine if these excess deaths are preventable is warranted.

Trophic control changes with season and nutrient loading in lakes.

Experiments have revealed much about top-down and bottom-up control in ecosystems, but manipulative experiments are limited in spatial and temporal scale. To obtain a more nuanced understanding of trophic control over large scales, we explored long-term time-series data from 13 globally distributed lakes and used empirical dynamic modelling to quantify interaction strengths between zooplankton and phytoplankton over time within and across lakes. Across all lakes, top-down effects were associated with nutrients, switching from negative in mesotrophic lakes to positive in oligotrophic lakes. This result suggests that zooplankton nutrient recycling exceeds grazing pressure in nutrient-limited systems. Within individual lakes, results were consistent with a 'seasonal reset' hypothesis in which top-down and bottom-up interactions varied seasonally and were both strongest at the beginning of the growing season. Thus, trophic control is not static, but varies with abiotic conditions - dynamics that only become evident when observing changes over large spatial and temporal scales.

Living With, and Caring for, Congenital Heart Disease in Australia: Insights From the Congenital Heart Alliance of Australia and New Zealand Online Survey.

BACKGROUND: There is a paucity of data describing the day-to-day experiences of adult Australians personally living with or caring for a child born with congenital heart disease (CHD). Such data would be of great practical importance to inform health care initiatives to improve outcomes. METHODS: 588 men (38.3 ± 11.9 years) and women (39.6 ± 12.6 years, 78% of respondent patients) living with CHD and 1,091 adult carers (93% mothers) of children with CHD (median age 7.3 [IQR 3.5-13.3 years], 54% male), representing all Australian states and territories, responded to a comprehensive online survey designed and hosted by the Congenital Heart Alliance of Australia and New Zealand. Data on demographic factors, the nature of underlying CHD, interactions with health care services, psychological wellbeing and wider impacts of CHD were collected. RESULTS: Most respondents were able to identify the type of CHD they (29% with a simple lesion such atrial septal defect, 17% tetralogy of Fallot) or their child had (21% with a simple lesion, 15% tetralogy of Fallot), whilst 90% cases of CHD had undergone cardiac surgery. Patients with CHD were mostly employed (70%) or studying (8.8%), whilst 9.1% were receiving disability benefits. In terms of transition care, 52% of adult patients had been referred by a paediatric to adult cardiologist with 84% still actively managed by a specialist. Overall, 31% of patients with CHD sought emergency care and required >10 days sick leave in the past 12 months. Moreover, 71% and 55% of patients, respectively, reported recent feelings of anxiety/worry or depressive thoughts related to their CHD (61% sought professional assistance). Consistent with high levels of disruption to daily living, 59% of carer respondents (24%>10 days) had taken carer's leave in the past 12 months. CONCLUSIONS: These contemporary, self-reported, Australian data reveal the burden of living and caring for CHD from an adult's perspective. Survey respondents highlighted the potential disconnect between paediatric and adult CHD services and suggest an important, unmet need for dedicated health services/community care to cost-effectively manage high levels of health care utilisation coupled with associated psychological distress.

Assessment of care provision for hypertension at the emergency Department of an Urban Hospital in Mozambique.

BACKGROUND: Management of hypertension in Mozambique is poor, and rates of control are amongst the lowest in the world. Health system related factors contribute at least partially to this situation, particularly in settings where there is scarcity of resources to address the double burden of infectious and non-communicable diseases. This study aimed to assess the management of hypertension in an emergency department (ED). METHODS: During a pragmatic and prospective 30-day snapshot study (with 24 h surveillance) and random profiling of one-in-five presentations to the ED of Hospital Geral de Mavalane, Maputo, we assessed patient's flow and care, as well as health facility's infrastructure and resources through direct observation. Reports from pharmacy and laboratory stocks were used to assess availability of diagnostics and medicines needed for hypertension management. RESULTS: The 1911 hypertensive patients included in the study had several stops during their journey inside the health facility and followed a non-standardized care flow. No clinical protocols or algorithms for risk stratification of hypertension were available. Stock-outs of basic diagnostic tools for risk stratification and medicines were registered. The availability of medicines was 28% on average. CONCLUSIONS: Critical gaps in health facility readiness to address arterial hypertension seen in ED were uncovered, including lack of clinical protocols, insufficient availability of diagnostics and essential medicines, as well as low affordability of the families to guaranty continuum of care. Innovative financing mechanisms are needed to support the health system to address hypertension.

Have Traditional Heart Failure Management Programs Reached Their "Use by" Date? Time to Apply More Nuanced Care.

PURPOSE OF REVIEW: To determine the current evidence supporting the otherwise proven heart failure management programs (HFMPs) in the setting of an increasingly older and more complex patient population. RECENT FINDINGS: Attempts to replace proven face-to-face, multidisciplinary management of HF with remote management techniques (including telemedicine and implantable remote monitoring devices) have yielded mixed results. This may well reflect the clinical cascade effect of greater surveillance paradoxically leading to worse health outcomes as well as a narrow focus on HF alone in patients with clinically significant multimorbidity. Concurrently, there is preliminary evidence that the increasing phenomenon of HF and multimorbidity in older patients is undermining the otherwise positive impact of "traditional" HFMPs. A more nuanced approach to determining who would benefit from what form of HF management, including the integration of remote surveillance techniques, is required.

Malignant and Benign Phenotypes of Multimorbidity in Heart Failure: Implications for Clinical Practice.

BACKGROUND: The impact of different patterns of multimorbidity in heart failure (HF) on health outcomes is unknown. OBJECTIVES: The aim of this study was to test the hypothesis that, independent of the extent of comorbidity, there are distinctive phenotypes of multimorbidity that convey an increased risk for premature mortality in patients hospitalized with HF. METHODS: We analyzed the clinical profile and health outcomes of 787 patients hospitalized with HF participating in a multidisciplinary HF management program with a minimum 12-month follow-up. A Classification and Regression Tree model was applied to explore the distinctive combinations of 10 most prevalent concurrent conditions (other than coronary artery disease and hypertension) associated with 12-month all-cause mortality. RESULTS: Mean (SD) age was 74 (12) years (59% men), and 65% had left ventricular systolic dysfunction. Most patients (88%) had 3 or more comorbid conditions, with a mean of 4.3 concurrent conditions in addition to HF. A total of 248 patients (32%) died (median, 663 [IQR, 492-910] days), including 142 deaths (18%) within 12 months. Patients with concurrent dysrhythmia, anemia, and respiratory disease experienced significantly higher 12-month all-cause mortality than those without these conditions (36.1% vs 3.6%, respectively; hazard ratio, 6.1 [95% confidence interval, 2.0-19.1]). Overall, this "malignant" phenotype of multimorbidity was associated with not only a markedly increased risk of all-cause mortality but also more unplanned readmissions, longer inpatient stays, and highest costs in the short (30-day) and longer terms when compared with more "benign" phenotypes of multimorbidity. CONCLUSIONS: We found a differential pattern of health outcomes according to pattern of comorbidity present in older patients hospitalized with HF and exposed to postdischarge, multidisciplinary management.

Physical and biological characteristics of multi drug resistance (MDR): An integral approach considering pH and drug resistance in cancer.

The role of the Warburg effect in cancer remains to be elucidated with a resurgence in research efforts over the past decade. Why a cancer cell would prefer to use energy inefficient glycolysis, leading to an alteration of pH both inside and outside of the cell, remains to be uncovered. The development of MDR represents a major challenge in the treatment of cancer and it is explained, so far, by the over expression of drug transporters such as the well-known and archetypal P-glycoprotein (Pgp). However, controversies exist regarding the function of Pgp in multi-drug resistance. We suggest here that Pgp-mediated MDR relies fundamentally on pH alterations mediated by the Warburg effect. Furthermore, we propose that the use of proton pump and/or transporters inhibitors (PPIs/PTIs) in cancer are key to controlling both MDR, i.e. sensitize tumors to antineoplastic agents, and drug-related adverse effects.

The National Echocardiography Database Australia (NEDA): Rationale and methodology.

The National Echocardiography Database Australia (NEDA) is a new echocardiography database collecting digital measurements on both a retrospective and prospective basis. To date, echocardiographic data from 435,133 individuals (aged 61.6 ±â€¯17.9 years) with linkage to 59,725 all-cause deaths during a median of 40 months follow-up have been collected. These data will inform a number of initial analyses focusing on pulmonary hypertension, aortic stenosis and the role of artificial intelligence to facilitate accurate diagnoses of cardiac abnormalities.

Transient endothelial dysfunction induced by sugar-sweetened beverage consumption may be attenuated by a single bout of aerobic exercise.

BACKGROUND: This study assessed whether aerobic exercise would attenuate microvascular endothelial dysfunction induced by commercial sugar-sweetened beverage (SSB) consumption. METHODS: Eleven healthy males participated in this randomized, single-blind crossover study. Cutaneous microvascular endothelial function was assessed using laser speckle contrast imaging coupled with post-occlusive reactive hyperemia before and after a) consumption of water; b) consumption of a commercial SSB; c) 30min of aerobic exercise followed by water consumption; and d) 30 minutes of aerobic exercise followed by SSB consumption. Blood glucose and arterial pressure responses were also monitored. Volumes of water and SSB consumed (637.39±29.15 mL) were individualized for each participant, ensuring SSB consumption delivered 1 g of sucrose per kg of body weight. Exercise was performed at 75% of the maximal oxygen uptake heart rate. RESULTS: Compared to water consumption, the commercial SSB elevated blood glucose concentrations in both sedentary (4.69±0.11 vs. 7.47±0.28 mmol/L, P<0.05) and exercised states (4.95±0.13 vs. 7.93±0.15 mmol/L, P<0.05). However, the decrease in microvascular endothelial function observed following sedentary SSB consumption, expressed as the percentage increase from baseline (208.60±22.40 vs. 179.83±15.80%, P=0.01) and the change in peak hyperemic blood flux from basal to post-intervention assessments (-0.04±0.03 vs. -0.12±0.02 ΔCVC, P=0.01), was attenuated following 30min of aerobic exercise. CONCLUSIONS: To our knowledge, this is the first study to provide evidence that a single bout of aerobic exercise may prevent transient SSB-mediated microvascular endothelial dysfunction.

Effects of Sugar-Sweetened Beverage Consumption on Microvascular and Macrovascular Function in a Healthy Population.

OBJECTIVE: To assess vascular function during acute hyperglycemia induced by commercial sugar-sweetened beverage (SSB) consumption and its effect on underlying mechanisms of the nitric oxide pathway. APPROACH AND RESULTS: In a randomized, single-blind, crossover trial, 12 healthy male participants consumed 600 mL (20 oz.) of water or a commercial SSB across 2 visits. Endothelial and vascular smooth muscle functions were assessed in the microcirculation using laser speckle contrast imaging coupled with iontophoresis and in the macrocirculation using brachial artery ultrasound with flow- and nitrate-mediated dilation. Compared with water, SSB consumption impaired microvascular and macrovascular endothelial function as indicated by a decrease in the vascular response to acetylcholine iontophoresis (208.3±24.3 versus 144.2±15.7%, P<0.01) and reduced flow-mediated dilation (0.019±0.002 versus 0.014±0.002%/s, P<0.01), respectively. Systemic vascular smooth muscle remained preserved. Similar decreases in endothelial function were observed during acute hyperglycemia in an in vivo rat model. However, function was fully restored by treatment with the antioxidants, N-acetylcysteine and apocynin. In addition, ex vivo experiments revealed that although the production of reactive oxygen species was increased during acute hyperglycemia, the bioavailability of nitric oxide in the endothelium was decreased, despite no change in the activation state of endothelial nitric oxide synthase. CONCLUSIONS: To our knowledge, this is the first study to assess the vascular effects of acute hyperglycemia induced by commercial SSB consumption alone. These findings suggest that SSB-mediated endothelial dysfunction is partly due to increased oxidative stress that decreases nitric oxide bioavailability. CLINICAL TRIAL REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=366442&isReview=true. Australian New Zealand Clinical Trials Registry Number: ACTRN12614000614695.

Multimorbidity and the Risk of All-Cause 30-Day Readmission in the Setting of Multidisciplinary Management of Chronic Heart Failure: A Retrospective Analysis of 830 Hospitalized Patients in Australia.

BACKGROUND: Multimorbidity has an adverse effect on health outcomes in hospitalized individuals with chronic heart failure (CHF), but the modulating effect of multidisciplinary management is unknown. OBJECTIVE: The aim of this study was to test the hypothesis that increasing morbidity would independently predict an increasing risk of 30-day readmission despite multidisciplinary management of CHF. METHODS: We studied patients hospitalized for any reason with heart failure receiving nurse-led, postdischarge multidisciplinary management. We profiled a matrix of expected comorbidities involving the most common coexisting conditions associated with CHF and examined the relationship between multimorbidity and 30-day all-cause readmission. RESULTS: A total of 830 patients (mean age 73 ± 13 years and 65% men) were assessed. Multimorbidity was common, with an average of 6.6 ± 2.4 comorbid conditions with sex-based differences in prevalence of 4 of 10 conditions. Within 30 days of initial hospitalization, 216 of 830 (26%) patients were readmitted for any reason. Greater multimorbidity was associated with increasing readmission (4%-44% for those with 0-1 to 8-9 morbid conditions; adjusted odds ratio, 1.25; 95% confidence interval, 1.13-1.38) for each additional condition. Three distinct classes of patient emerged: class 1-diabetes, metabolic, and mood disorders; class 2-renal impairment; and class 3-low with relatively fewer comorbid conditions. Classes 1 and 2 had higher 30-day readmission than class 3 did (adjusted P < .01 for both comparisons). CONCLUSIONS: These data affirm that multimorbidity is common in adult CHF inpatients and in potentially distinct patterns linked to outcome. Overall, greater multimorbidity is associated with a higher risk of 30-day all-cause readmission despite high-quality multidisciplinary management. More innovative approaches to target-specific clusters of multimorbidity are required to improve health outcomes in affected individuals.

Impact of Nurse-Led, Multidisciplinary Home-Based Intervention on Event-Free Survival Across the Spectrum of Chronic Heart Disease: Composite Analysis of Health Outcomes in 1226 Patients From 3 Randomized Trials.

BACKGROUND: We sought to determine the overall impact of a nurse-led, multidisciplinary home-based intervention (HBI) adapted to hospitalized patients with chronic forms of heart disease of varying types. METHODS AND RESULTS: Prospectively planned, combined, secondary analysis of 3 randomized trials (1226 patients) of HBI were compared with standard management. Hospitalized patients presenting with heart disease but not heart failure, atrial fibrillation but not heart failure, and heart failure, as well, were recruited. Overall, 612 and 614 patients, respectively, were allocated to a home visit 7 to 14 days postdischarge by a cardiac nurse with follow-up and multidisciplinary support according to clinical need or standard management. The primary outcome of days-alive and out-of-hospital was examined on an intention-to-treat basis. During 1371 days (interquartile range, 1112-1605) of follow-up, 218 patients died and 17 917 days of hospital stay were recorded. In comparison with standard management, HBI patients achieved significantly prolonged event-free survival (90.1% [95% confidence interval, 88.2-92.0] versus 87.2% [95% confidence interval, 85.1-89.3] days-alive and out-of-hospital; P=0.020). This reflected less all-cause mortality (adjusted hazard ratio, 0.67; 95% confidence interval, 0.50-0.88; P=0.005) and unplanned hospital stay (median, 0.22 [interquartile range, 0-1.3] versus 0.36 [0-2.1] days/100 days follow-up; P=0.011). Analyses of the differential impact of HBI on all-cause mortality showed significant interactions (characterized by U-shaped relationships) with age (P=0.005) and comorbidity (P=0.041); HBI was most effective for those aged 60 to 82 years (59%-65% of individual trial cohorts) and with a Charlson Comorbidity Index Score of 5 to 8 (36%-61%). CONCLUSIONS: These data provide further support for the application of postdischarge HBI across the full spectrum of patients being hospitalized for chronic forms of heart disease. CLINICAL TRIAL REGISTRATION: URL: http://www.anzctr.org.au. Unique identifiers: 12610000221055, 12608000022369, 12607000069459.

Pattern and Outcome of Heart Failure-Related Hospitalization Over 5 Years in a Remote Australian Population: A Retrospective Administrative Data Cohort of 617 Indigenous and non-Indigenous Cases.

OBJECTIVE: The aim of this work was to understand the pattern and outcomes for heart failure (HF)-related hospitalization among Indigenous and non-Indigenous patients living in Central Australia. METHODS AND RESULTS: A retrospective analysis of administrative data for patients presenting with a primary or secondary diagnosis of HF to Central Australia's Alice Springs Hospital during 2008-2012 was performed. The population rate of admission and subsequent outcomes (including mortality and readmission) during the 5-year study period were examined. A total of 617 patients, aged 55.8 ± 17.5 years and 302 (49%) female constituted the study cohort. The 446 Indigenous patients (72%) were significantly younger (50.8 ± 15.9 vs 68.7 ± 14.9; P < .001) and clinically more complex compared with the non-Indigenous patients. Annual prevalence of any HF hospitalization was markedly higher in the Indigenous population (1.9%, 95% CI 1.7-2.1) compared with the non-Indigenous population (0.5%, 95% CI 0.4-0.6); the greatest difference being for women. Overall, non-Indigenous patients had poorer outcomes and were significantly more likely to die (P < .0001), but this was largely driven by age differences. Alternatively, Indigenous patients were significantly more likely to have a higher number of hospitalizations, although indigeneity was not a predictor for 30- or 365-day rehospitalization from the index admission. CONCLUSION: The pattern of HF among Indigenous Australians in Central Australia is characterized by a younger population with more clinically complex cases and greater health care utilization.

Assessing cutaneous microvascular function with iontophoresis: Avoiding non-specific vasodilation.

AIM: Iontophoresis of vasoactive agents is commonly used to assess cutaneous microvascular reactivity. However, it is known that iontophoresis can be limited by confounding non-specific vasodilatory effects. Despite this, there is still no standardization of protocols or data expression. Therefore, this study evaluated commonly used protocols of iontophoresis by assessing each for evidence of non-specific vasodilatory effects and examined the reproducibility of those protocols that are free of non-specific responses. METHODS: Twelve healthy participants were administered doses of acetylcholine (ACh) 1-2% and sodium nitroprusside (SNP) 1%, diluted in sodium chloride 0.9% or deionized water, and insulin 100U/mL in a sterile diluent using iontophoresis coupled with laser speckle contrast imaging (LSCI). Increases in blood flux at a control electrode, containing the diluent only, indicated a non-specific response. Reproducibility of iontophoresis protocols that were free of non-specific vasodilatory effects were subsequently compared to that of post-occlusive reactive hyperemia (PORH), used as a standard, in 20 healthy participants. RESULTS: Iontophoresis of ACh or SNP in sodium choloride (0.02mA for 200 and 400s, respectively) and ACh in deionized water (0.1mA for 30s) mediated the least non-specific vasodilatory effects. Microvascular responses to insulin were mediated mainly by non-specific effects. Compared to PORH, the intraday and interday reproducibility for iontophoresis of ACh and SNP (0.02mA for 200 and 400s, respectively) with LSCI was weaker, but still deemed good to excellent when data was expressed, in perfusion units or cutaneous vascular conductance, as the absolute peak blood flux response to the vascular reactivity test or as the change in blood flux between peak and baseline values. CONCLUSION: This study provides updated recommendations for assessing cutaneous microvascular function with iontophoresis.

Better Indigenous Risk stratification for Cardiac Health study (BIRCH) protocol: rationale and design of a cross-sectional and prospective cohort study to identify novel cardiovascular risk indicators in Aboriginal Australian and Torres Strait Islander adults.

BACKGROUND: Of the estimated 10-11 year life expectancy gap between Indigenous (Aboriginal and Torres Strait Islander people) and non-Indigenous Australians, approximately one quarter is attributable to cardiovascular disease (CVD). Risk prediction of CVD is imperfect, but particularly limited for Indigenous Australians. The BIRCH (Better Indigenous Risk stratification for Cardiac Health) project aims to identify and assess existing and novel markers of early disease and risk in Indigenous Australians to optimise health outcomes in this disadvantaged population. It further aims to determine whether these markers are relevant in non-Indigenous Australians. METHODS/DESIGN: BIRCH is a cross-sectional and prospective cohort study of Indigenous and non-Indigenous Australian adults (≥ 18 years) living in remote, regional and urban locations. Participants will be assessed for CVD risk factors, left ventricular mass and strain via echocardiography, sleep disordered breathing and quality via home-based polysomnography or actigraphy respectively, and plasma lipidomic profiles via mass spectrometry. Outcome data will comprise CVD events and death over a period of five years. DISCUSSION: Results of BIRCH may increase understanding regarding the factors underlying the increased burden of CVD in Indigenous Australians in this setting. Further, it may identify novel markers of early disease and risk to inform the development of more accurate prediction equations. Better identification of at-risk individuals will promote more effective primary and secondary preventive initiatives to reduce Indigenous Australian health disadvantage.