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Iron deficiency (ID) is highly prevalent in patients with heart failure (HF) but its impact on prognosis in HF with preserved ejection fraction (HFpEF) remains unclear. We assessed whether ID defined by soluble transferrin receptor (sTfR) criteria is independently associated with all-cause mortality in patients with HFpEF, and evaluated its comparative prognostic performance to ID definitions in common clinical use.Data were analyzed from 788 patients (36% HFpEF) in a prospective multicenter HF cohort study. Baseline plasma samples were analyzed with respect to 4 definitions of ID: sTfR of ≥1.59 mg/L (IDID defined by sTfR criteria is independently associated with all-cause mortality in patients with HFpEF. Poor concordance between ID definitions suggests that iron biomarkers do not reflect the same pathological process in the complex relationship between iron and HF. Therefore, which definition should guide iron replacement needs further evaluation.

AIMS: Chronic obstructive pulmonary disease (COPD) is a frequent comorbidity in patients with heart failure (HF). We assessed the influence of COPD on circulating levels and prognostic value of three HF biomarkers: N-terminal pro-B-type natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), and soluble suppression of tumorigenesis-2 (sST2).METHODS: Individual data from patients with chronic HF, known COPD status, NT-proBNP and hs-TnT values (n = 8088) were analysed. A subgroup (n = 3414) had also sST2 values.RESULTS: Patients had a median age of 66 years (interquartile interval 57-74), 77% were men and 82% had HF with reduced ejection fraction. NT-proBNP, hs-TnT and sST2 were 1207 ng/l (487-2725), 17 ng/l (9-31) and 30 ng/ml (22-44), respectively. Patients with COPD (n = 1249, 15%) had higher NT-proBNP (P = 0.042) and hs-TnT (P CONCLUSIONS: Among patients with HF, those with COPD have higher NT-proBNP and hs-TnT, but not sST2. All these biomarkers yield prognostic significance regardless of the COPD status.

Objectives The goal of this study was to assess the predictive power of N-terminal pro–B-type natriuretic peptide (NT-proBNP) and the decision cutoffs in heart failure (HF) across body mas...

Aims The importance of iron deficiency (ID) in heart failure with preserved ejection fraction (HFpEF) is unknown. In HF with reduced ejection fraction (HFrEF), ID is reported as an independent predictor of mortality in HF although not all published studies agree. Different definitions of ID have been assessed, and the natural history of untreated ID not established, which may explain the conflicting results. This study aimed to assess the relationship between ID and mortality in HFpEF, clarify which definition of ID correlates best with outcomes in HFrEF, and determine the prognostic importance of change in ID status over time. Methods and results Analyses were conducted on data from 1563 patients participating in a prospective international cohort study comparing HFpEF with HFrEF. Plasma samples from baseline and 6 month visits were analysed for the presence of ID. Two ID definitions were evaluated: IDFerritin = ‘ferritin

Heart failure is a common healthcare problem associated with high morbidity and mortality. The burden of heart failure is changing; increases secondary to an ageing population may be offset by improved primary cardiovascular prevention and advances in heart failure therapies. In this review we evaluate recent international trends in heart failure incidence, morbidity and mortality. Although the age standardised incidence of heart failure has been decreasing since 2000, the incidence in those age groups

BACKGROUND Even modest reductions in blood pressure (BP) can have an important impact on population-level morbidity and mortality from cardiovascular disease. There are 2 promising approaches: the SaltSwitch smartphone app, which enables users to scan the bar code of a packaged food using their smartphone camera and receive an immediate, interpretive traffic light nutrition label on-screen alongside a list of healthier, lower-salt options in the same food category; and reduced-sodium salts (RSSs), which are an alternative to regular table salt that are lower in sodium and higher in potassium but have a similar mouthfeel, taste, and flavor. OBJECTIVE Our aim was to determine whether a 12-week intervention with a sodium-reduction package comprising the SaltSwitch smartphone app and an RSS could reduce urinary sodium excretion in adults with high BP. METHODS A 2-arm parallel randomized controlled trial was conducted in New Zealand (target n=326). Following a 2-week baseline period, adults who owned a smartphone and had high BP (≥140/85 mm Hg) were randomized in a 1:1 ratio to the intervention (SaltSwitch smartphone app + RSS) or control (generic heart-healthy eating information from The Heart Foundation of New Zealand). The primary outcome was 24-hour urinary sodium excretion at 12 weeks estimated via spot urine. Secondary outcomes were urinary potassium excretion, BP, sodium content of food purchases, and intervention use and acceptability. Intervention effects were assessed blinded using intention-to-treat analyses with generalized linear regression adjusting for baseline outcome measures, age, and ethnicity. RESULTS A total of 168 adults were randomized (n=84, 50% per group) between June 2019 and February 2020. Challenges associated with the COVID-19 pandemic and smartphone technology detrimentally affected recruitment. The adjusted mean difference between groups was 547 (95% CI −331 to 1424) mg for estimated 24-hour urinary sodium excretion, 132 (95% CI −1083 to 1347) mg for urinary potassium excretion, −0.66 (95% CI −3.48 to 2.16) mm Hg for systolic BP, and 73 (95% CI −21 to 168) mg per 100 g for the sodium content of food purchases. Most intervention participants reported using the SaltSwitch app (48/64, 75%) and RSS (60/64, 94%). SaltSwitch was used on 6 shopping occasions, and approximately 1/2 tsp per week of RSS was consumed per household during the intervention. CONCLUSIONS In this randomized controlled trial of a salt-reduction package, we found no evidence that dietary sodium intake was reduced in adults with high BP. These negative findings may be owing to lower-than-anticipated engagement with the trial intervention package. However, implementation and COVID-19–related challenges meant that the trial was underpowered, and it is possible that a real effect may have been missed. CLINICALTRIAL Australian New Zealand Clinical Trials Registry ACTRN12619000352101; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377044 and Universal Trial U1111-1225-4471

Background: The TOPCAT trial (Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial) suggested clinical benefits of spironolactone treatment among patients with heart failure with preserved ejection fraction enrolled in the Americas. However, a comprehensive assessment of biologic pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction has not been performed. Methods: We conducted aptamer-based proteomic analysis utilizing 5284 modified aptamers to 4928 unique proteins on plasma samples from TOPCAT participants from the Americas (n=164 subjects with paired samples at baseline and 1 year) to identify proteins and pathways impacted by spironolactone therapy in heart failure with preserved ejection fraction. Mean percentage change from baseline was calculated for each protein. Additionally, we conducted pathway analysis of proteins altered by spironolactone. Results: Spironolactone therapy was associated with proteome-wide significant changes in 7 proteins. Among these, CARD18 (caspase recruitment domain-containing protein 18), PKD2 (polycystin 2), and PSG2 (pregnancy-specific glycoprotein 2) were upregulated, whereas HGF (hepatic growth factor), PLTP (phospholipid transfer protein), IGF2R (insulin growth factor 2 receptor), and SWP70 (switch-associated protein 70) were downregulated. CARD18, a caspase-1 inhibitor, was the most upregulated protein by spironolactone (−0.5% with placebo versus +66.5% with spironolactone, P Conclusions: Proteomic analysis in the TOPCAT trial revealed proteins and pathways altered by spironolactone, including the caspase inhibitor CARD18 and multiple pathways that involved collagens. In addition to effects on fibrosis, our studies suggest potential antiapoptotic effects of spironolactone in heart failure with preserved ejection fraction, a hypothesis that merits further exploration.

Background. Each year, approximately 5000 New Zealanders are admitted to hospital with first-time acute coronary syndrome (ACS). The Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) is a prospective longitudinal cohort study embedded within the All New Zealand Acute Coronary Syndrome Quality Improvement (ANZACS-QI) registry in six hospitals. The objective of MENZACS is to examine the relationship between clinical, genomic, and cardiometabolic markers in relation to presentation and outcomes post-ACS. Methods. Patients with first-time ACS are enrolled and study-specific research data is collected alongside the ANZACS-QI registry. The research blood samples are stored for future genetic/biomarker assays. Dietary information is collected with a food frequency questionnaire and information about physical activity, smoking, and stress is also collected via questionnaire. Detailed family history, ancestry, and ethnicity data are recorded on all participants. Results. During the period between 2015 and 2019, there were 2015 patients enrolled. The mean age was 61 years, with 60% of patients aged Conclusion. MENZACS represents a cohort with optimal contemporary management and will be a significant epidemiological bioresource for the study of environmental and genetic factors contributing to ACS in New Zealand’s multi-ethnic environment. The study will utilise clinical, nutritional, lifestyle, genomic, and biomarker analyses to explore factors influencing the progression of coronary disease and develop risk prediction models for health outcomes.

Background Even modest reductions in blood pressure (BP) can have an important impact on population-level morbidity and mortality from cardiovascular disease. There are 2 promising approaches: the SaltSwitch smartphone app, which enables users to scan the bar code of a packaged food using their smartphone camera and receive an immediate, interpretive traffic light nutrition label on-screen alongside a list of healthier, lower-salt options in the same food category; and reduced-sodium salts (RSSs), which are an alternative to regular table salt that are lower in sodium and higher in potassium but have a similar mouthfeel, taste, and flavor. Objective Our aim was to determine whether a 12-week intervention with a sodium-reduction package comprising the SaltSwitch smartphone app and an RSS could reduce urinary sodium excretion in adults with high BP. Methods A 2-arm parallel randomized controlled trial was conducted in New Zealand (target n=326). Following a 2-week baseline period, adults who owned a smartphone and had high BP (≥140/85 mm Hg) were randomized in a 1:1 ratio to the intervention (SaltSwitch smartphone app + RSS) or control (generic heart-healthy eating information from The Heart Foundation of New Zealand). The primary outcome was 24-hour urinary sodium excretion at 12 weeks estimated via spot urine. Secondary outcomes were urinary potassium excretion, BP, sodium content of food purchases, and intervention use and acceptability. Intervention effects were assessed blinded using intention-to-treat analyses with generalized linear regression adjusting for baseline outcome measures, age, and ethnicity. Results A total of 168 adults were randomized (n=84, 50% per group) between June 2019 and February 2020. Challenges associated with the COVID-19 pandemic and smartphone technology detrimentally affected recruitment. The adjusted mean difference between groups was 547 (95% CI −331 to 1424) mg for estimated 24-hour urinary sodium excretion, 132 (95% CI −1083 to 1347) mg for urinary potassium excretion, −0.66 (95% CI −3.48 to 2.16) mm Hg for systolic BP, and 73 (95% CI −21 to 168) mg per 100 g for the sodium content of food purchases. Most intervention participants reported using the SaltSwitch app (48/64, 75%) and RSS (60/64, 94%). SaltSwitch was used on 6 shopping occasions, and approximately 1/2 tsp per week of RSS was consumed per household during the intervention. Conclusions In this randomized controlled trial of a salt-reduction package, we found no evidence that dietary sodium intake was reduced in adults with high BP. These negative findings may be owing to lower-than-anticipated engagement with the trial intervention package. However, implementation and COVID-19–related challenges meant that the trial was underpowered, and it is possible that a real effect may have been missed. Trial Registration Australian New Zealand Clinical Trials Registry ACTRN12619000352101; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=377044 and Universal Trial U1111-1225-4471

ObjectiveThe Multi-Ethnic New Zealand Study of Acute Coronary Syndromes (MENZACS) was established to investigate the drivers of secondary events after first-time acute coronary syndrome (ACS), including addressing inequitable outcomes by ethnicity. Herein, the first clinical outcomes and prognostic modelling approach are reported.MethodsFirst, in 28 176 New Zealanders with first-time ACS from a national registry, a clinical summary score for predicting 1-year death/cardiovascular readmission was created using Cox regression of 20 clinical variables. This score was then calculated in the 2015 participant MENZACS study to represent clinical risk. In MENZACS, Cox regression was used to assess N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a prognostic marker for death/cardiovascular readmission in four models, adjusting for (1) age and sex; (2) age, sex, ethnicity; (3) clinical summary score; (4) clinical summary score and ethnicity.ResultsOf the 2015 MENZACS participants (mean age 61 years, 79% male, 73% European, 14% Māori, 5% Pacific people), 2003 were alive at discharge. Of the 2003, 416 (20.8%) experienced all-cause death/cardiovascular readmission over a median of 3.5 years. In a simple model, age, male sex, Māori ethnicity and NT-proBNP levels were significant predictors of outcome. After adjustment for the clinical summary score, which includes age and sex, NT-proBNP and ethnicity were no longer statistically significant: log2(NT-proBNP) hazard ratio (HR) 1.03, 95% confidence interval (95% CI) 0.98 to 1.08, p=0.305; Māori ethnicity HR 1.26, 95% CI 0.97 to 1.62, p=0.084.ConclusionsIn 2015 patients with first-time ACS, recurrent events were common (20.8%). Increasing NT-proBNP levels and Māori ethnicity were predictors of death/cardiovascular readmission, but not after adjustment for the 20 clinical risk factors represented by the clinical summary score.Trial registration numberACTRN12615000676516.

This is the peer reviewed version of the following article: Aimo, A., Januzzi, J.L., Vergaro, G., Richards, A.M., Lam, C.S.P., Latini, R. ... Emdin, M. (2020). Circulating levels and prognostic value of soluble ST2 in heart failure are less influenced by age than N-terminal pro-B-type natriuretic peptide and high-sensitivity troponin T, European Journal of Heart Failure, which has been published in final form at https://doi.org/10.1002/ejhf.1701. . This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions. Aims - N‐terminal pro‐B‐type natriuretic peptide (NT‐proBNP), high‐sensitivity troponin T (hs‐TnT) and soluble suppression of tumorigenesis‐2 (sST2) predict outcome in chronic heart failure (HF). We assessed the influence of age on circulating levels and prognostic significance of these biomarkers. Methods and results - Individual data from 5301 patients with chronic HF and NT‐proBNP, hs‐TnT, and sST2 data were evaluated. Patients were stratified according to age: Conclusions - Soluble ST2 is less influenced by age than NT‐proBNP or hs‐TnT; all these biomarkers predict outcome regardless of age. The use of age‐ and outcome‐specific cut‐offs of NT‐proBNP, hs‐TnT and sST2 allows more accurate risk stratification than NT‐proBNP alone or the combination of NT‐proBNP and hs‐TnT.

BackgroundPrognostic biomarkers for patients admitted for a myocardial infarction (MI) episode are of great interest for risk stratification and follow-up care after discharge. Multi-omics analysis is a standard approach for the discovery of diagnostic and prognostic biomarkers, but few studies have evaluated the prognostic potential of molecular markers in combination with echocardiographic imaging variables.MethodsWe measured the plasma proteome and lipidome in patients discharged from an acute MI and followed for secondary outcomes in New Zealand for a median time of 4.85 years (CDCS, N=741 for network inference, N=464 for predictive analysis) and in Singapore for a median time of 2.0 years (IMMACULATE, N=190 for validation). Using a network-based integrative analysis framework iOmicsPASS+, we mapped proteins, lipids, echocardiographic imaging variables and clinical biomarkers to a unified network and identified predictive subnetwork signatures of major adverse cardiac events (MACE) and heart failure hospitalization (HFH) in CDCS, with validation in IMMACULATE.ResultsSpecific plasma proteins and lipids showed direct connections to cardiac imaging variables in the network. The gold standard biomarker, NT-proBNP, remained one of the best prognostic marker of MACE and HFH, but a number of plasma proteins involved in extracellular matrix organization, chemotaxis, inflammation, and apoptosis were also strong predictors of both outcomes. Hub proteins of subnetwork signatures were enriched in the heart, arteries, kidneys, liver and lungs. BMP10, CAPG, EFEMP1, FSTL3, RSPO4, and RELT were those directly connected to the echocardiographic variables and natriuretic peptides. In particular, EFEMP1 and FSTL3 in combination with diastolic function (E/e’) were strongly predictive of HFH in both CDCS (AUC 0.78, 95%CI 0.72-0.83) and IMMACULATE (AUC 0.72, 0.61-0.84).ConclusionsOur integrative analysis revealed competing signatures beyond established biomarkers of post-MI HFH, comprised of plasma proteins correlated with impaired diastolic function after the primary MI episode.

Background Optimizing quality of life (QoL) is a key priority in the management of heart failure (HF). Hypothesis To investigate ethnic differences in QoL and its association with 1-year survival among patients with HF. Methods A prospective nationwide cohort (n = 1070, mean age: 62 years, 24.5% women) of Chinese (62.3%), Malay (26.7%) and Indian (10.9%) ethnicities from Singapore, QoL was assessed using the Minnesota Living with HF Questionnaire (MLHFQ) at baseline and 6 months. Patients were followed for all-cause mortality. Results At baseline, Chinese had a lower (better) mean MLHFQ total score (29.1 +/- 21.6) vs Malays (38.5 +/- 23.9) and Indians (41.7 +/- 24.5);P

Aims Limited evidence exists on sex-related differences in clinical value of biomarkers in chronic heart failure (HF). We aimed to define plasma levels, determinants, and optimal prognostic cut-offs of soluble suppression of tumourigenesis-2 (sST2), high-sensitivity troponin T (hs-TnT), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) in female and male chronic HF patients. Methods and results Individual data of patients from the BIOS (Biomarkers In Heart Failure Outpatient Study) Consortium with sST2, hs-TnT, and NT-proBNP measured were analysed. The primary endpoint was a composite of 1-year cardiovascular death and HF hospitalization. The secondary endpoints were 5-year cardiovascular and all-cause death. The cohort included 4540 patients (age: 67 ± 12 years, LVEF 33 ± 13%, 1111 women, 25%). Women showed lower sST2 (24 vs. 27 ng/ml, P Conclusions In patients with chronic HF, levels of sST2 and hs-TnT, but not of NT-proBNP are lower in women. Lower sST2 and hs-TnT and higher NT-proBNP cut-offs for risk stratification could be used in women.

Background Data on rehospitalizations for heart failure (HF) in Asia are scarce. We sought to determine the burden and predictors of HF (first and recurrent) rehospitalizations and all‐cause mortality in patients with HF and preserved versus reduced ejection fraction (preserved EF, ≥50%; reduced EF, Methods and Results Patients with symptomatic (stage C) chronic HF were followed up for death and recurrent HF hospitalizations for 1 year. Predictors of HF hospitalizations or all‐cause mortality were examined with Cox regression for time to first event and other methods for recurrent events analyses. Among 1666 patients with HF with preserved EF (mean age, 68±12 years; 50% women), and 4479 with HF with reduced EF (mean age, 61±13 years; 22% women), there were 642 and 2302 readmissions, with 28% and 45% attributed to HF, respectively. The 1‐year composite event rate for first HF hospitalization or all‐cause death was 11% and 21%, and for total HF hospitalization and all‐cause death was 17.7 and 38.7 per 100 patient‐years in HF with preserved EF and HF with reduced EF, respectively. In HF with preserved EF, consistent independent predictors of these clinical end points included enrollment as an inpatient, Southeast Asian location, and comorbid chronic kidney disease or atrial fibrillation. The same variables were predictive of outcomes in HF with reduced EF except atrial fibrillation, and also included Northeast Asian location, older age, elevated heart rate, decreased systolic blood pressure, diabetes, smoking, and non‐usage of beta blockers. Conclusions One‐year HF rehospitalization and mortality rates were high among Asian patients with HF. Predictors of outcomes identified in this study could aid in risk stratification and timely interventions. Registration URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01633398.

Background Image-based methods that combine catheterisation with non-concurrent cardiac magnetic resonance (CMR) imaging data and echocardiography (echo) is gaining more interest than the conductance catheter method to derive pressure-volume loops (PVLs) due to improved accuracy and accessibility of LV volume quantification [1–3]. However, accurate temporal registration between LV pressure and volume is not well developed. Purpose We propose a framework for temporally registering invasive LV and aortic pressures (LVP and AOP) acquired during left heart catheterisation with real time 3D echocardiography (RT3DE) to generate in vivo PVLs in a group of heart transplant (HTx) recipients. Methods 25 orthotopic HTx recipients (mean age: 54±8 years and 7 female) indicated for routine coronary assessment were recruited for invasive hemodynamic measurement and RT3DE imaging. A fluid-filled pigtail catheter was used to measure LVP and AOP with simultaneous electrocardiogram (ECG) over several (9–15) heartbeats. Within an hour of catheterisation, single-beat transthoracic RT3DE of the LV was performed from the apical window in a left lateral decubitus position. Imaging parameters were optimized for each patient to maximize the temporal resolution (between 15–41 imaging frames per cycle). We developed a piecewise linear temporal scaling method based on cardiac events (end-diastole (ED), end of isovolumic contraction (eIVC), end-systole (ES), end of isovolumic relaxation (eIVR), and diastasis (DS)) of RT3DE and haemodynamic measurement to resample the LVP at the RT3DE imaging frames between the cardiac events to construct PVLs (Fig. 1a). Geometric LV models were manually fitted at ED and ES, followed by automatic tracking across intermediary frames to estimate LV volume over the entire cardiac cycle (Fig. 1b). The temporally aligned pressure values were further averaged to find the beat-averaged LV PVL (Fig. 1c). Results Based on the number of cardiac cycles selected for haemodynamic analysis, multiple in vivo PVLs were constructed for each patient. A beat-averaged PVL was also computed for each patient (Fig.1d). With the exception of one case, the beat-averaged PVLs exhibited classically representative shape with distinct isovolumic contraction and isovolumic relaxation phases. The individual diastolic PVRs for all patients are shown in Fig.1e, with beat-to-beat variation observed in most patients. For some cases, the variation manifested as an offset in LVP, whereas changes in the diastolic PVR slope were observed in other cases. Conclusion Temporal alignment scheme based on cardiac events allowed accurate derivation of patient-specific in vivo PVLs from catheterization and RT3DE measurements. Application to heart transplant recipients revealed beat-to-beat variation of haemodynamic state. Further analysis of the diastolic PVRs will allow quantification of chamber stiffness for HTx recipients. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Research Council of New Zealand Patient-specific PVLs

Background Global longitudinal strain (GLS) has emerged as a sensitive index of left ventricular (LV) systolic function with greater prognostic value than LV ejection fraction (LVEF) in a variety of cardiac disorders. While GLS is routinely derived from 2D speckle tracking echocardiography (STE) and feature tracking in cardiac magnetic resonance (CMR) imaging, calculation of strain via 3D geometric modelling enables analyses of deformation that are independent of 2D image plane constraints. Purpose We sought to compare longitudinal strain measurements extracted from geometric 3D analysis of CMR against values obtained from conventional 2D-STE. Methods Consecutive 2D-echocardiography (2D-echo) and steady-state free precession multiplanar cine CMR scans were performed in 80 prospectively recruited participants (48 healthy controls with LVEF range 53–74%, 30 patients with non-ischaemic cardiac disease with LVEF range 25–77%, and 2 heart transplant recipients with LVEF 53% and 58%), Results GLS measured by 2D-STE ranged between −6.5% and −27.9% for the study population. A two-way mixed-effects intraclass correlation coefficient (ICC) for absolute agreement of 0.820 (95% CI: [0.720, 0.885]) demonstrated good correlation between average GLS obtained from 2D-STE and CMR. A Bland-Altman analysis revealed a minimal bias ( Conclusions Fully automated calculation of LV GLS can be obtained from geometric 3D CMR analysis. Average peak GLS from cine CMR exhibits good agreement with 2D-STE, despite showing only moderate agreement at each LV wall. The increased discrepancy in regional longitudinal strain may be attributed to subjective plane positioning in 2D-echo, which can be expected to improve with advances in 3D-STE. The calculation of GLS by 3D geometric modelling may enhance the diagnostic value of routine cine CMR examinations for LV systolic function assessment. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Health Research Council (HRC) of New Zealand and National Heart Foundation (NHF) of New Zealand Figure 1. Bland-Altman analysisTable I. Regional correlations

Background In New Zealand (NZ) approximately 10,000 people experience an acute coronary syndrome (ACS) annually. Little is known about the diets of people who present with first ACS. Methods The Multi-Ethnic NZ study of Acute Coronary Syndromes (MENZACS) is a multi-centre, longitudinal cohort study of patients with first-time ACS. At baseline, patients complete a validated short food frequency questionnaire (FFQ) asking about dietary intakes in the 12 months preceding their event. Participants are followed up for rehospitalisation and mortality. Results Here we present the dietary intakes of the 2,015 participants enrolled into MENZACS. We excluded 90 participants who did not start the FFQ and 42 participants who had extreme energy intakes. For men (n = 1489), the median energy intake was 8637 kJ, and the median percentage of energy from carbohydrate, protein, fat, and saturated fat were 40.3%, 17.9%, 34.7% and 17.8%, respectively. For women (n = 394), the median energy intake was 7499 kJ, and the median percentage of energy from carbohydrate, protein, fat and saturated fat were 40.3%, 18.4%, 35.6%, and 18.0%, respectively. Conclusions Both men and women reported high saturated fat intakes in the year preceding their first ACS. Future work will examine dietary predictors of rehospitalisation and mortality, as well as analyse baseline blood samples for Lipoprotein(a) and lipidomics. Key messages Patients in hospital with first time ACS are able to complete a short food frequency questionnaire, with little missing data.

ObjectiveStudies indicate that age-standardised heart failure (HF) incidence has been decreasing internationally; however, contrasting trends in different age groups have been reported, with rates increasing in younger people and decreasing in the elderly. We aimed to describe age-specific trends in HF incidence in New Zealand (NZ).MethodsIn this nationwide data linkage study, we used routinely collected hospitalisation data to identify incident HF hospitalisations in NZ residents aged ≥20 years between 2006 and 2018. Age-specific and age-standardised incidence rates were calculated for each calendar year. Joinpoint regression was used to compare incidence trends.Results116 113 incident HF hospitalisations were identified over the 13-year study period. Between 2006 and 2013, age-standardised incidence decreased from 403 to 323 per 100 000 (annual percentage change (APC) −2.6%, 95% CI −3.6 to −1.6%). This reduction then plateaued between 2013 and 2018 (APC 0.8%, 95% CI −0.8 to 2.5%). Between 2006 and 2018, rates in individuals aged 20–49 years old increased by 1.5% per year (95% CI 0.3 to 2.7%) and decreased in those aged ≥80 years old by 1.2% per year (95% CI −1.7 to −0.7%). Rates in individuals aged 50–79 years old initially declined from 2006 to 2013, and then remained stable or increased from 2013 to 2018. The proportion of HF hospitalisations associated with ischaemic heart disease decreased from 35.1% in 2006 to 28.0% in 2018.ConclusionHF remains an important problem in NZ. The decline in overall incidence has plateaued since 2013 due to increasing rates of HF in younger age groups despite an ongoing decline in the elderly.

Aims Inflammation plays an important role in cardiovascular disease (CVD) development. The NOD-like receptor protein-3 (NLRP3) inflammasome contributes to the development of atherosclerosis in animal models. Components of the NLRP3 inflammasome pathway such as interleukin-1β can therapeutically be targeted. Associations of genetically determined inflammasome-mediated systemic inflammation with CVD and mortality in humans are unknown. Methods and results We explored the association of genetic NLRP3 variants with prevalent CVD and cardiovascular mortality in 538 167 subjects on the individual participant level in an explorative gene-centric approach without performing multiple testing. Functional relevance of single-nucleotide polymorphisms on NLRP3 inflammasome activation has been evaluated in monocyte-enriched peripheral blood mononuclear cells (PBMCs). Genetic analyses identified the highly prevalent (minor allele frequency 39.9%) intronic NLRP3 variant rs10754555 to affect NLRP3 gene expression. rs10754555 carriers showed significantly higher C-reactive protein and serum amyloid A plasma levels. Carriers of the G allele showed higher NLRP3 inflammasome activation in isolated human PBMCs. In carriers of the rs10754555 variant, the prevalence of coronary artery disease was significantly higher as compared to non-carriers with a significant interaction between rs10754555 and age. Importantly, rs10754555 carriers had significantly higher risk for cardiovascular mortality during follow-up. Inflammasome inducers (e.g. urate, triglycerides, apolipoprotein C3) modulated the association between rs10754555 and mortality. Conclusion The NLRP3 intronic variant rs10754555 is associated with increased systemic inflammation, inflammasome activation, prevalent coronary artery disease, and mortality. This study provides evidence for a substantial role of genetically driven systemic inflammation in CVD and highlights the NLRP3 inflammasome as a therapeutic target.

BACKGROUND Heart failure (HF) is a leading cause of morbidity and mortality worldwide. Plasma concentrations of B-type natriuretic peptide (BNP) or its amino terminal congener (NT-proBNP) are used for HF diagnosis and risk stratification. Because BNP concentrations are inexplicably lowered in obese patients, we investigated the relationship between proBNP glycosylation, plasma NT-proBNP, and body mass index (BMI) in HF patients. METHODS Three assays were developed to distinguish between total proBNP (glycosylated plus nonglycosylated proBNP), proBNP not glycosylated at threonine 71 (NG-T71), and proBNP not glycosylated in the central region (NG-C). Intraassay and interassay CVs were RESULT Applying these assays and an NT-proBNP assay to plasma samples from 106 healthy volunteers and 238 HF patients determined that concentrations [median (interquartile range)] of proBNP, NG-T71, and NT-proBNP were greater in HF patients compared with controls [300 (44–664), 114 (18–254), and 179 (880–3459) ng/L vs 36 (18–229), 36 (18–175), and 40 (17–68) ng/L, respectively; all P < 0.012]. NG-C was undetectable in most samples. ProBNP concentrations in HF patients with BMI more or less than 30 kg/m2 were not different (P = 0.85), whereas HF patients with BMI >30 kg/m2 had lower NT-proBNP and NG-T71 concentrations (P < 0.003) and higher proBNP/NT-proBNP and proBNP/NG-T71 ratios (P = 0.001 and P = 0.02, respectively) than those with BMI CONCLUSIONS Increased BMI is associated with decreased concentrations of proBNP not glycosylated at T71. Decreased proBNP substrate amenable to processing could partially explain the lower NT-proBNP and BNP concentrations observed in obese individuals, including those presenting with HF.

Background Clinicians need improved tools to better identify nonacute heart failure with preserved ejection fraction (HFpEF). Objectives The purpose of this study was to derive and validate circulating microRNA signatures for nonacute heart failure (HF). Methods Discovery and validation cohorts (N = 1,710), comprised 903 HF and 807 non-HF patients from Singapore and New Zealand (NZ). MicroRNA biomarker panel discovery in a Singapore cohort (n = 546) was independently validated in a second Singapore cohort (Validation 1; n = 448) and a NZ cohort (Validation 2; n = 716). Results In discovery, an 8-microRNA panel identified HF with an area under the curve (AUC) 0.96, specificity 0.88, and accuracy 0.89. Corresponding metrics were 0.88, 0.66, and 0.77 in Validation 1, and 0.87, 0.58, and 0.74 in Validation 2. Combining microRNA panels with N-terminal pro–B-type natriuretic peptide (NT-proBNP) clearly improved specificity and accuracy from AUC 0.96, specificity 0.91, and accuracy 0.90 for NT-proBNP alone to corresponding metrics of 0.99, 0.99, and 0.93 in the discovery and 0.97, 0.96, and 0.93 in Validation 1. The 8-microRNA discovery panel distinguished HFpEF from HF with reduced ejection fraction with AUC 0.81, specificity 0.66, and accuracy 0.72. Corresponding metrics were 0.65, 0.41, and 0.56 in Validation 1 and 0.65, 0.41, and 0.62 in Validation 2. For phenotype categorization, combined markers achieved AUC 0.87, specificity 0.75, and accuracy 0.77 in the discovery with corresponding metrics of 0.74, 0.59, and 0.67 in Validation 1 and 0.72, 0.52, and 0.68 in Validation 2, as compared with NT-proBNP alone of AUC 0.71, specificity 0.46, and accuracy 0.62 in the discovery; with corresponding metrics of 0.72, 0.44, and 0.57 in Validation 1 and 0.69, 0.48, and 0.66 in Validation 2. Accordingly, false negative (FN) (81% Singapore and all NZ FN cases were HFpEF) as classified by a guideline-endorsed NT-proBNP ruleout threshold, were correctly reclassified by the 8-microRNA panel in the majority (72% and 88% of FN in Singapore and NZ, respectively) of cases. Conclusions Multi-microRNA panels in combination with NT-proBNP are highly discriminatory and improved specificity and accuracy in identifying nonacute HF. These findings suggest potential utility in the identification of nonacute HF, where clinical assessment, imaging, and NT-proBNP may not be definitive, especially in HFpEF.