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International audience; Aims: Spironolactone is currently used in a large proportion of patients with heart failure and preserved ejection fraction (HFpEF), yet its effect on cardiac structure and function in a large population has not been well established. The aim of this study was to evaluate the impact of spironolactone on key echocardiographic parameters in HFpEF.Methods and results: An individual-patient-data meta-analysis of three randomized trials (HOMAGE, Aldo-DHF, and TOPCAT) was performed comparing spironolactone (9-12 month exposure) to placebo (or control) for the changes in left atrial volume index (LAVi), left ventricular mass index (LVMi), interventricular septum (IVS) thickness, E/e' ratio, and left ventricular ejection fraction (LVEF) among patients with stage B (HOMAGE) or C (Aldo-DHF and TOPCAT) HFpEF. Analysis of covariance was used to test the effect of spironolactone on echocardiographic changes. A total of 984 patients were included in this analysis: 452 (45.9%) from HOMAGE, 398 (40.4%) from Aldo-DHF, and 134 (13.6%) from TOPCAT. The pooled-cohort patient's median age was 71 (66-77) years and 39% were women. Median LAVi was 29 (24-35) ml/m2 , LVMi 100 (84-118) g/m2 , IVS thickness 12 (10-13) mm, E/e' ratio 11 (9-13), and LVEF 64 (59-69)%. Spironolactone reduced LAVi by -1.1 (-2.0 to -0.1) ml/m2 (p = 0.03); LVMi by -3.6 (-6.4 to -0.8) g/m2 (p = 0.01); IVS thickness by -0.2 (-0.3 to -0.1) mm (p = 0.01); E/e' ratio by -1.3 (-2.4 to -0.2) (p = 0.02); and increased LVEF by 1.7 (0.8-2.6)% (p < 0.01). No treatment-by-study heterogeneity was found except for E/e' ratio with a larger effect in Aldo-DHF and TOPCAT (interaction p < 0.01).Conclusions: Spironolactone improved cardiac structure and function of patients with HFpEF.

Background Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-recommended medical therapy (GRMT) in heart failure (HF). Our aim was to evaluate the evolution and impact of MR after GRMT in the Biology study to Tailored treatment in chronic heart failure (BIOSTAT-CHF). Methods A retrospective post-hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Results Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate-severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate-severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint (unadjusted hazard ratio [HR], 2.03; 95% confidence interval [CI], 1.57–2.63; p p Conclusions Among patients with HF undergoing GRMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate-severe MR after GRMT was associated with worse outcome. Graphical abstract

Background: We sought to identify protein biomarkers of new-onset heart failure (HF) in 3 independent cohorts (HOMAGE cohort [Heart Omics and Ageing], ARIC study [Atherosclerosis Risk in Communities], and FHS [Framingham Heart Study]) and assess if and to what extent they improve HF risk prediction compared to clinical risk factors alone. Methods: A nested case-control design was used with cases (incident HF) and controls (without HF) matched on age and sex within each cohort. Plasma concentrations of 276 proteins were measured at baseline in ARIC (250 cases/250 controls), FHS (191/191), and HOMAGE cohort (562/871). Results: In single protein analysis, after adjusting for matching variables and clinical risk factors (and correcting for multiple testing), 62 proteins were associated with incident HF in ARIC, 16 in FHS, and 116 in HOMAGE cohort. Proteins associated with incident HF in all cohorts were BNP (brain natriuretic peptide), NT-proBNP (N-terminal pro-B-type natriuretic peptide), eukaryotic translation initiation factor 4E-BP1 (4E-binding protein 1), hepatocyte growth factor (HGF), Gal-9 (galectin-9), TGF-alpha (transforming growth factor alpha), THBS2 (thrombospondin-2), and U-PAR (urokinase plasminogen activator surface receptor). The increment in C -index for incident HF based on a multiprotein biomarker approach, in addition to clinical risk factors and NT-proBNP, was 11.1% (7.5%–14.7%) in ARIC, 5.9% (2.6%–9.2%) in FHS, and 7.5% (5.4%–9.5%) in HOMAGE cohort, all P Conclusions: A multiprotein biomarker approach improves prediction of incident HF when added to natriuretic peptides and clinical risk factors.

Aims Albuminuria is common in patients with heart failure and associated with worse outcomes. The underlying pathophysiological mechanism of albuminuria in heart failure is still incompletely understood. The association of clinical characteristics and biomarker profile with albuminuria in patients with heart failure with both reduced and preserved ejection fractions were evaluated. Methods and results Two thousand three hundred and fifteen patients included in the index cohort of BIOSTAT-CHF were evaluated and findings were validated in the independent BIOSTAT-CHF validation cohort (1431 patients). Micro-albuminuria and macro-albuminuria were defined as urinary albumin–creatinine ratio (UACR) >30 mg/gCr and >300 mg/gCr in spot urines, respectively. The prevalence of micro- and macro-albuminuria was 35.4% and 10.0%, respectively. Patients with albuminuria had more severe heart failure, as indicated by inclusion during admission, higher New York Heart Association functional class, more clinical signs and symptoms of congestion, and higher concentrations of biomarkers related to congestion, such as biologically active adrenomedullin, cancer antigen 125, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) (all P < 0.001). The presence of albuminuria was associated with increased risk of mortality and heart failure (re)hospitalization in both cohorts. The strongest independent association with log UACR was found for log NT-proBNP (standardized regression coefficient 0.438, 95% confidence interval 0.35–0.53, P < 0.001). Hierarchical clustering analysis demonstrated that UACR clusters with markers of congestion and less with indices of renal function. The validation cohort yielded similar findings. Conclusion In patients with new-onset or worsening heart failure, albuminuria is consistently associated with clinical, echocardiographic, and circulating biomarkers of congestion.

BackgroundThe consequences of teenage childbearing on the health of mothers and children, and on girls’ schooling have been documented in many studies. The objectives of this study are to: 1) examine trends and differentials in teenage motherhood in Cameroon, with a distinction between premarital and marital teenage pregnancy; and 2) investigate trends and differentials in the length of time to marriage following a premarital teenage pregnancy.MethodsWe use data from five demographic and health surveys (DHS) conducted in Cameroon between 1991 and 2018. Teenage pregnancy, defined as first pregnancy occurring before the age of 20 years, is recode as a trichotomous variable (0 = No teenage pregnancy; 1 = marital teenage pregnancy; 2 = premarital teenage pregnancy). Time from first premarital teenage pregnancy to first marriage is analyzed as a continuous variable.ResultsThe percentage of women who experienced a marital teenage pregnancy declined from 39.6% to 26.4% between 1991 and 2018. After an initial drop between 1991 and 2004, premarital teenage pregnancy stabilized at about 25%. Women with intermediate levels of schooling were more likely to experience a premarital pregnancy than those with no schooling or higher secondary/tertiary education. The median length of time to first marriage following a premarital teenage pregnancy rose from 16 months in 1991 to 45 months in 2018. Further analysis suggests that marriage may be a more severe barrier to continued schooling than motherhood and that the desire to continue schooling is an important reason for postponing marriage for women who have given birth.Conclusion and recommendationsBesides strengthening interventions to curb adolescent pregnancy, efforts should be made to support families, communities and schools to help adolescent mothers return to school, prevent future unintended pregnancies, and delay further family formation. Accessibility to youth-friendly FP/RH services should be addressed.

Aims Chronic heart failure (CHF) is a systemic syndrome with a poor prognosis and a need for novel therapies. We investigated whether whole blood transcriptomic profiling can provide new mechanistic insights into cardiovascular (CV) mortality in CHF. Methods and results Transcriptome profiles were generated at baseline from 944 CHF patients from the BIOSTAT-CHF study, of whom 626 survived and 318 died from a CV cause during a follow-up of 21 months. Multivariable analysis, including adjustment for cell count, identified 1153 genes (6.5%) that were differentially expressed between those that survived or died and strongly related to a validated clinical risk score for adverse prognosis. The differentially expressed genes mainly belonged to five non-redundant pathways: adaptive immune response, proteasome-mediated ubiquitin-dependent protein catabolic process, T-cell co-stimulation, positive regulation of T-cell proliferation, and erythrocyte development. These five pathways were selectively related (RV coefficients >0.20) with seven circulating protein biomarkers of CV mortality (fibroblast growth factor 23, soluble ST2, adrenomedullin, hepcidin, pentraxin-3, WAP 4-disulfide core domain 2, and interleukin-6) revealing an intricate relationship between immune and iron homeostasis. The pattern of survival-associated gene expression matched with 29 perturbagen-induced transcriptome signatures in the iLINCS drug-repurposing database, identifying drugs, approved for other clinical indications, that were able to reverse in vitro the molecular changes associated with adverse prognosis in CHF. Conclusion Systematic modelling of the whole blood protein-coding transcriptome defined molecular pathways that provide a link between clinical risk factors and adverse CV prognosis in CHF, identifying both established and new potential therapeutic targets.

AIMS: Myocardial infarction (MI) is among the commonest attributable risk factors for heart failure (HF). We compared clinical characteristics associated with the progression to HF in patients with or without a history of MI in the HOMAGE cohort and validated our results in UK Biobank. METHODS AND RESULTS: During a follow-up of 5.2 (3.5-5.9) years, 177 (2.4%) patients with prior MI and 370 (1.92%) patients without prior MI experienced HF onset in the HOMAGE cohort (n = 26 478, history of MI: n = 7241). Older age, male sex and higher heart rate were significant risk factors of HF onset in patients with and without prior MI. Lower renal function was more strongly associated with HF onset in patients with prior MI. Higher body mass index (BMI), systolic blood pressure and blood glucose were significantly associated with HF onset only in patients without prior MI (all p for interactions

Aims: \ud Left ventricular ejection fraction (LVEF) can provide haemodynamic information and may influence the response to spironolactone and other heart failure (HF) therapies. We aimed to study patient characteristics and circulating protein associations with LVEF, and whether LVEF influenced the response to spironolactone.\ud \ud Methods and results: \ud HOMAGE enrolled patients aged >60 years at high risk of developing HF with a LVEF ≥45%. Overall, 527 patients were randomized to either spironolactone or standard of care for ≈9 months, and 276 circulating proteins were measured using Olink® technology. A total of 364 patients had available LVEF determined by the Simpson's biplane method. The respective LVEF tertiles were: tertile 1: 65% (n = 121). Patients with a LVEF >65% had smaller left ventricular chamber size and volumes, and lower natriuretic peptide levels. Compared to patients with a LVEF 65% had higher levels of circulating c-c motif chemokine ligand-23 and interleukin-8, and lower levels of tissue plasminogen activator, brain natriuretic peptide (BNP), S100 calcium binding protein A12, and collagen type I alpha 1 chain (COL1A1). Spironolactone significantly reduced the circulating levels of BNP and COL1A1 without significant treatment-by-LVEF heterogeneity: BNP change β = −0.36 log2 and COL1A1 change β = −0.16 log2 (p 0.1 for both). Spironolactone increased LVEF from baseline to month 9 by 1.1% (p = 0.007).\ud \ud Conclusion: \ud Patients with higher LVEF had higher circulating levels of chemokines and inflammatory markers and lower levels of stretch, injury, and fibrosis markers. Spironolactone reduced the circulating levels of natriuretic peptides and type 1 collagen, and increased LVEF.

The health hazards of short inter-birth intervals are severe in Cameroon. One-quarter of inter-birth intervals are less than 24 months and the probability of death before age 5 for children born after a short interval is double that associated with intervals of 36-47 months. We examine the risk of an unintended pregnancy in the 18 months following childbirth in Cameroon, taking into account the protective effects of lactational amenorrhea, delayed resumption of sex as well as contraceptive use.Data from 3007 postpartum women in the nationally representative 2018 Cameroon Demographic and Health Survey were used. Risk of an unintended pregnancy was defined from current status information on resumption of sex and menses, contraceptive use, desire for another child within 12 months, and, for the minority of pregnant women, whether the conception was intended. Predictors of risk, and of modern method use, were assessed by bivariate and multivariate analysis.In the first 6 postpartum months, only 8% of women were fully at risk (i.e., sex and menses resumed but no contraceptive use), rising to 24% at 6-11 postpartum months, and further to 30% at months 12-17. Though 89% wanted to delay the next birth by at least 1 year, only 17% were currently using a modern method. Menstruating women were much more likely to be users than amenorrheic women: 27% versus 15% at months 12-17 postpartum. Urban and better educated women recorded higher contraceptive use but lower protection from other factors than rural, less educated women, with the net result that risk differed little across these population strata. Uptake of maternal and child health (MCH) services was high but only one-third of women had discussed family planning at a facility visit during the preceding 12 months.These results underscore the need for improved postpartum family planning services by means of closer integration with mainstream health services. In view of evidence from other sources of heavy workload and weak motivation of health staff, this will require strong leadership. A related priority is to increase the number of staff trained in provision of long-acting methods, such as implants.We use information from mothers with a child under the age of 18 months, who were interviewed in a national survey conducted in 2018. We examine risk of an unintended pregnancy, using data on factors that protect against risk, namely delayed resumption of sex and menses, breastfeeding and contraceptive use. Among mothers with an infant aged less than 6 months, very few were at risk mainly because they had not resumed sex. Among those with an infant aged 6–11 months, 26% had still not resumed sex and an equal proportion was partially protected by delayed resumption of menses. Only 17% were protected by use of a modern contraceptive method, leaving 24% fully at risk. Among those with a child aged 12–18 months, 30% were fully at risk. As expected, well educated, urban women were more likely to use contraception than less privileged women but less likely to be protected by delayed resumption of sex and menses, with the consequence that pregnancy-risk was similar. Though three-quarters of mothers had taken their child for vaccination on three or more occasions, only one-third had discussed family planning with a health provider at a visit to a facility in the previous 12 months. The need for improved contraceptive services for mothers with young children is clear. Short intervals between births are common in Cameroon and these threaten the health of mothers and children. It is equally clear that closer integration of family planning into mainstream health services is needed.

Introduction: \ud Limited data exist regarding the prognostic relevance of changes in left atrial (LA) dimensions in patients with heart failure (HF). We assessed changes in LA dimension and their relation with outcomes after optimization of guideline-directed medical therapy (GDMT) in patients with worsening HF.\ud \ud Methods and Results: \ud LA diameter was assessed at baseline and 9 months after GDMT optimization in 632 patients (mean age 65.8±12.1 years, 22.3% female) enrolled in BIOSTAT-CHF. LA adverse remodelling (LAAR) was defined as an increase in LA diameter on transthoracic echocardiography between baseline and 9 months. After the 9-month visit, patients were followed for a median of 13 further months. LAAR was observed in 247 patients (39%). Larger baseline LA diameter (odds ratio (OR) 0.90; 95% confidence interval (95% CI) 0.87 – 0.93; p

Aims Few data are available regarding changes in mitral regurgitation (MR) severity with guideline-directed medical therapy (GDMT) in heart failure (HF). We evaluated the evolution and impact of MR after GDMT in the BIOlogy Study to TAilored Treatment in Chronic Heart Failure (BIOSTAT-CHF). Methods and results A retrospective post hoc analysis was performed on HF patients from BIOSTAT-CHF with available data on MR status at baseline and at 9-month follow-up after GRMT optimization. The primary endpoint was a composite of all-cause death or HF hospitalization. Among 1022 patients with data at both time-points, 462 (45.2%) had moderate-severe MR at baseline and 360 (35.2%) had it at 9-month follow-up. Regression of moderate–severe MR from baseline to 9 months occurred in 192/462 patients (41.6%) and worsening from baseline to moderate–severe MR at 9 months occurred in 90/560 patients (16.1%). The presence of moderate-severe MR at 9 months, independent from baseline severity, was associated with an increased risk of the primary endpoint [unadjusted hazard ratio (HR), 2.03; 95% confidence interval (CI): 1.57–2.63; P Conclusions Among patients with HF undergoing GDMT optimization, ACEi/ARB up-titration and HFpEF were associated with MR improvement, and the presence of moderate–severe MR after GRMT was associated with worse outcome.

Intro: Randomised controlled trials are the gold standard method for assessing treatment effects. However, those who participate in trials of heart failure (HF) are usually highly selected (by the protocol, investigators and patient-choice) and, on average, younger and with fewer comorbidities than those encountered in clinical practice. Trials can be calibrated to better reflect routine clinical practice by re-estimating treatment effects after adjusting for differences in characteristics between trial and target populations, whilst maintaining the principle of randomisation. Methods: Using individual-level participant data, we calibrated 2 trials of HF with predominantly reduced left ventricular ejection fraction (HFrEF) - COMET (100% HFrEF) and DIG (87% HFrEF) and 1 trial of HF with preserved left ventricular ejection fraction TOPCAT - to 8,012 HF patients from a Scottish HF register using two methods - one regression-based and one using inverse propensity score weighting (IPSW). Results: Compared to register patients, trial participants had lower furosemide doses and were younger (mean (standard deviation) age 73 (12) years vs 62 (11), 64 (11) and 69 (10) years) with higher eGFR (59 (23) vs 67 (21), 62 (21) and 68 (18) ml/min/1.73m 2 for register vs COMET, DIG and TOPCAT respectively). For each trial, effect estimates from uncalibrated and calibrated analyses were similar (Figure 1; e.g. odds ratios in COMET for all-cause mortality were 0.83 (0.74, 0.93), 0.71 (0.58, 0.88) and 0.97 (0.72, 1.27) in the uncalibrated, IPSW and regression-based analyses). The calibrated estimates for all three trials were at most 1.5-fold less precise (i.e., 1.5-fold wider 95% confidence intervals) than the standard estimates. Conclusions: Calibration may be used to estimate the applicability of trial findings to populations typically encountered in clinical settings, with only small reductions in the precision of the effect estimates, and without breaking randomisation.

ObjectivesTo investigate severe COVID-19 risk by occupational group.MethodsBaseline UK Biobank data (2006-10) for England were linked to SARS-CoV-2 test results from Public Health England (16 March to 26 July 2020). Included participants were employed or self-employed at baseline, alive and aged less than 65 years in 2020. Poisson regression models adjusted sequentially for baseline demographic, socioeconomic, work-related, health, and lifestyle-related risk factors to assess risk ratios (RRs) for testing positive in hospital or death due to COVID-19 by three occupational classification schemes (including Standard Occupation Classification 2000).ResultsOf 120,075 participants, 271 had severe COVID-19. Relative to non-essential workers, healthcare workers (RR 7.43, 95% CI:5.52,10.00), social and education workers (RR 1.84, 95% CI:1.21,2.82) and other essential workers (RR=1.60, 95% CI:1.05,2.45) had higher risk of severe COVID-19. Using more detailed groupings, medical support staff (RR 8.70, 95% CI:4.87,15.55), social care (RR 2.46, 95% CI:1.47,4.14) and transport workers (RR= 2.20, 95% CI:1.21,4.00) had highest risk within the broader groups. Compared to white non-essential workers, non-white non-essential workers had a higher risk (RR 3.27, 95% CI: 1.90,5.62) and non-white essential workers had the highest risk (RR 8.34, 95% CI:5.17,13.47). Using SOC2000 major groups, associate professional and technical occupations, personal service occupations and plant and machine operatives had higher risk, compared to managers and senior officials.ConclusionsEssential workers have higher risk of severe COVID-19. These findings underscore the need for national and organizational policies and practices that protect and support workers with elevated risk of severe COVID-19.Trial registration-N/AWhat is already known on this topicEssential workers have a higher exposure to the SARS-CoV-2 virus due to the nature of their work.In comparison to non-essential workers, healthcare workers appear to have a higher risk of SARS-CoV-2 infection.What this study addsHealthcare workers had a more than seven-fold higher risk of severe COVID-19; those working in social care and transport occupations had a two-fold higher risk.Adjusting for potential confounding and mediating variables did not fully account for the differences in the observed risk amongst most occupational groups.Non-white essential workers had the highest risk of severe COVID-19 infection.How might this impact on policy or clinical practice in the foreseeable future?Our findings reinforce the need for adequate health and safety arrangements and provision of PPE, particularly in the health and social care sectors, and highlight the need for national and organizational policies and practices that protect and support workers with elevated risk of SARS-CoV-2 infection.

Total cholesterol and high-density lipoprotein cholesterol (HDL-C) measurements are central to cardiovascular disease (CVD) risk assessment, but there is continuing debate around the utility of other lipids for risk prediction.Participants from UK Biobank without baseline CVD and not taking statins, with relevant lipid measurements (n=346 686), were included in the primary analysis. An incident fatal or nonfatal CVD event occurred in 6216 participants (1656 fatal) over a median of 8.9 years. Associations of nonfasting lipid measurements (total cholesterol, HDL-C, non-HDL-C, direct and calculated low-density lipoprotein cholesterol [LDL-C], and apolipoproteins [Apo] A1 and B) with CVD were compared using Cox models adjusting for classical risk factors, and predictive utility was determined by the C-index and net reclassification index. Prediction was also tested in 68 649 participants taking a statin with or without baseline CVD (3515 CVD events).ApoB, LDL-C, and non-HDL-C were highly correlated (r0.90), while HDL-C was strongly correlated with ApoA1 (r=0.92). After adjustment for classical risk factors, 1 SD increase in ApoB, direct LDL-C, and non-HDL-C had similar associations with composite fatal/nonfatal CVD events (hazard ratio, 1.23, 1.20, 1.21, respectively). Associations for 1 SD increase in HDL-C and ApoA1 were also similar (hazard ratios, 0.81 [both]). Adding either total cholesterol and HDL-C, or ApoB and ApoA, to a CVD risk prediction model (C-index, 0.7378) yielded similar improvement in discrimination (C-index change, 0.0084; 95% CI, 0.0065, 0.0104, and 0.0089; 95% CI, 0.0069, 0.0109, respectively). Once total and HDL-C were in the model, no further substantive improvement was achieved with the addition of ApoB (C-index change, 0.0004; 95% CI, 0.0000, 0.0008) or any measure of LDL-C. Results for predictive utility were similar for a fatal CVD outcome, and in a discordance analysis. In participants taking a statin, classical risk factors (C-index, 0.7118) were improved by non-HDL-C (C-index change, 0.0030; 95% CI, 0.0012, 0.0048) or ApoB (C-index change, 0.0030; 95% CI, 0.0011, 0.0048). However, adding ApoB or LDL-C to a model already containing non-HDL-C did not further improve discrimination.Measurement of total cholesterol and HDL-C in the nonfasted state is sufficient to capture the lipid-associated risk in CVD prediction, with no meaningful improvement from addition of apolipoproteins, direct or calculated LDL-C.

International audience; Background Identifying the mechanistic pathways potentially associated with incident heart failure (HF) may provide a basis for novel preventive strategies. Methods and Results To identify proteomic biomarkers and the potential underlying mechanistic pathways that may be associated with incident HF defined as the first hospitalization for HF, a nested-matched case-control design was used with cases (incident HF) and controls (without HF) selected from 3 cohorts (>20 000 individuals). Controls were matched on cohort, follow-up time, age, and sex. Two independent sample sets (a discovery set with 286 cases and 591 controls and a replication set with 276 cases and 280 controls) were used to discover and replicate the findings. Two hundred fifty-two circulating proteins in the plasma were studied. Adjusting for the matching variables age, sex, and follow-up time (and correcting for multiplicity of tests), 89 proteins were found to be associated with incident HF in the discovery phase, of which 38 were also associated with incident HF in the replication phase. These 38 proteins pointed to 4 main network clusters underlying incident HF: (1) inflammation and apoptosis, indicated by the expression of the TNF (tumor necrosis factor)-family members; (2) extracellular matrix remodeling, angiogenesis and growth, indicated by the expression of proteins associated with collagen metabolism, endothelial function, and vascular homeostasis; (3) blood pressure regulation, indicated by the expression of natriuretic peptides and proteins related to the renin-angiotensin-aldosterone system; and (4) metabolism, associated with cholesterol and atherosclerosis. Conclusions Clusters of biomarkers associated with mechanistic pathways leading to HF were identified linking inflammation, apoptosis, vascular function, matrix remodeling, blood pressure control, and metabolism. These findings provide important insight on the pathophysiological mechanisms leading to HF. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02556450.

Nitroxyl (HNO) causes post-translational modification of thiol proteins. In animal models, the HNO donor BMS-986231 causes vasodilation and has inotropic and lusitropic actions. We compared the effects of BMS-986231 to nitroglycerin (NTG) or placebo on cardiac performance in patients with chronic

Heart failure guidelines recommend up-titration of angiotensin-converting enzyme (ACE) inhibitor/angiotensin receptor blockers (ARBs), beta-blockers, and mineralocorticoid receptor antagonists (MRAs) to doses used in randomized clinical trials, but these recommended doses are often not reached. Up-titration may, however, not be necessary in all patients.This study sought to establish the role of blood biomarkers to determine which patients should or should not be up-titrated.Clinical outcomes of 2,516 patients with worsening heart failure from the BIOSTAT-CHF (BIOlogy Study to Tailored Treatment in Chronic Heart Failure) were compared between 3 theoretical treatment scenarios: scenario A, in which all patients are up-titrated to50% of recommended doses; scenario B, in which patients are up-titrated according to a biomarker-based treatment selection model; and scenario C, in which no patient is up-titrated to50% of recommended doses. The study conducted multivariable Cox regression using 161 biomarkers and their interaction with treatment, weighted for treatment-indication bias to estimate the expected number of deaths or heart failure hospitalizations at 24 months for all 3 scenarios.Estimated death or hospitalization rates in 1,802 patients with available (bio)markers were 16%, 16%, and 26%, respectively, in the ACE inhibitor/ARB up-titration scenarios A, B, and C. Similar rates for beta-blocker and MRA up-titration scenarios A, B, and C were 23%, 19%, and 24%, and 12%, 11%, and 24%, respectively. If up-titration was successful in all patients, an estimated 9.8, 1.3, and 12.3 events per 100 treated patients could be prevented at 24 months by ACE inhibitor/ARB, beta-blocker, and MRA therapy, respectively. Similar numbers were 9.9, 4.7, and 13.1 if up-titration treatment decision was based on a biomarker-based treatment selection model.Up-titrating patients with heart failure based on biomarker values might have resulted in fewer deaths or hospitalizations compared with a hypothetical scenario in which all patients were successfully up-titrated.

Hyperkalaemia is a common co-morbidity in patients with heart failure with reduced ejection fraction (HFrEF). Whether it affects the use of renin-angiotensin-aldosterone system inhibitors and thereby negatively impacts outcome is unknown. Therefore, we investigated the association between potassium and uptitration of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) and its association with outcome.Out of 2516 patients from the BIOSTAT-CHF study, potassium levels were available in 1666 patients with HFrEF. These patients were sub-optimally treated with ACEi/ARB or beta-blockers and were anticipated and encouraged to be uptitrated. Potassium levels were available at inclusion and at 9 months. Outcome was a composite of all-cause mortality and heart failure hospitalization at 2 years. Patients' mean age was 67 ± 12 years and 77% were male. At baseline, median serum potassium was 4.3 (interquartile range 3.9-4.6) mEq/L. After 9 months, 401 (24.1%) patients were successfully uptitrated with ACEi/ARB. During this period, mean serum potassium increased by 0.16 ± 0.66 mEq/L (P 0.001). Baseline potassium was an independent predictor of lower ACEi/ARB dosage achieved [odds ratio 0.70; 95% confidence interval (CI) 0.51-0.98]. An increase in potassium was not associated with adverse outcomes (hazard ratio 1.15; 95% CI 0.86-1.53). No interaction on outcome was found between baseline potassium, potassium increase during uptitration, or potassium at 9 months and increased dosage of ACEi/ARB (PHigher potassium levels are an independent predictor of enduring lower dosages of ACEi/ARB. Higher potassium levels do not attenuate the beneficial effects of ACEi/ARB uptitration.

Proprotein convertase subtilisin/kexin type 9 (PCSK9) binds low-density lipoprotein receptor (LDLR), preventing its recycling. PCSK9 is a risk predictor and a biotarget in atherosclerosis progression.The aim of this study was to determine whether the PCSK9-LDLR axis could predict risk in patients with heart failure (HF).The BIOSTAT-CHF (Biology Study to Tailored Treatment in Chronic Heart Failure) is a multicenter, multinational, prospective, observational study that included patients with worsening HF signs and/or symptoms. The primary endpoints were all-cause mortality and the composite of mortality or unscheduled hospitalizations for HF. We implemented Cox proportional hazard regression to determine the simultaneously adjusted effect of PCSK9 and LDLR on both outcomes when added to the previously validated BIOSTAT-CHF risk scores.This study included 2,174 patients (mean age: 68 ± 12 years; 53.2% had a history of ischemic heart disease). Median (interquartile range) PCSK9 and LDLR levels were 1.81 U/ml (1.45 to 2.18) and 2.98 U/ml (2.45 to 3.53), respectively. During follow-up, 569 deaths (26.2%) and 896 (41.2%) composite endpoints were ascertained. A multivariable analysis, which included BIOSTAT-CHF risk scores, LDLR, and statin treatment as covariates, revealed a positive linear association between PCSK9 levels and the risk of mortality (hazard ratio [HR]: 1.24; 95% confidence interval [CI]: 1.04 to 1.49; p = 0.020) and the composite endpoint (HR: 1.21; 95% CI: 1.05 to 1.40; p = 0.010). A similar analysis for LDLR revealed a negative association with mortality (HR: 0.86; 95% CI: 0.76 to 0.98; p = 0.025) and the composite endpoint (HR: 0.92; 95% CI: 0.83 to 1.01; p = 0.087). Including PCSK9 and LDLR improved risk score performance.The PCSK9-LDLR axis was associated with outcomes in patients with HF. Future studies must assess whether PCSK9 inhibition will result in better outcomes in HF.

Heart failure with preserved (HFpEF) and mid-range ejection fraction (HFmrEF) are becoming the most prevalent forms of heart failure. Patients with HFpEF/HFmrEF in atrial fibrillation (AF) have poorer survival and quality of life, but the mechanism underpinning this is unknown. We sought to investigate the influence of AF on the haemodynamic profile of HFpEF/HFmrEF patients at rest and during exercise.We invasively measured central haemodynamics at rest and during symptom-limited supine bicycle exercise in HFpEF/HFmrEF patients, 35 in sinus rhythm and 20 in AF with matched left ventricular ejection fraction. At rest, AF patients had significantly increased pulmonary capillary wedge pressure, lower cardiac index and reduced left ventricular stroke work index, despite similar resting heart rate. Under resting conditions, calculated oxygen consumption and systemic arteriovenous oxygen gradient were not different between the two groups. During supine cycling at similar levels of workload, AF patients exhibited a reduced capacity to increase their oxygen consumption and this was accompanied by a persistently impaired cardiac index and left ventricular stroke work index.The adverse interaction of AF and HFpEF/HFmrEF may be accounted for by an adverse impact on left ventricular systolic function and peripheral oxygen kinetics.

Cardiac resynchronization therapy (CRT) reduces morbidity and mortality in patients with symptomatic heart failure and QRS prolongation but there is uncertainty about which patient characteristics predict short-term clinical response.In an individual patient meta-analysis of three double-blind, randomized trials, clinical composite score (CCS) at 6 months was compared in patients assigned to CRT programmed on or off. Treatment-covariate interactions were assessed to measure likelihood of improved CCS at 6 months. MIRACLE, MIRACLE ICD, and REVERSE trials contributed data for this analysis (n = 1591). Multivariable modelling identified QRS duration and left ventricular ejection fraction (LVEF) as predictors of CRT clinical response (P0.05). The odds ratio for a better CCS at 6 months increased by 3.7% for every 1% decrease in LVEF for patients assigned to CRT-on compared to CRT-off, and was greatest when QRS duration was between 160 and 180 ms.In symptomatic chronic heart failure patients (NYHA class II-IV), longer QRS duration and lower LVEF independently predict early clinical response to CRT.

The prognosis of patients hospitalized for worsening heart failure (HF) is well described, but not that of patients managed solely in non-acute settings such as primary care or secondary outpatient care. We assessed the distribution of HF across levels of healthcare, and assessed the prognostic differences for patients with HF either recorded in primary care (including secondary outpatient care) (PC), hospital admissions alone, or known in both contexts.This study was part of the CALIBER programme, which comprises linked data from primary care, hospital admissions, and death certificates for 2.1 million inhabitants of England. We identified 89 554 patients with newly recorded HF, of whom 23 547 (26%) were recorded in PC but never hospitalized, 30 629 (34%) in hospital admissions but not known in PC, 23 681 (27%) in both, and 11 697 (13%) in death certificates only. The highest prescription rates of ACE inhibitors, beta-blockers, and mineralocorticoid receptor antagonists was found in patients known in both contexts. The respective 5-year survival in the first three groups was 43.9% [95% confidence interval (CI) 43.2-44.6%], 21.7% (95% CI 21.1-22.2%), and 39.8% (95% CI 39.2-40.5%), compared with 88.1% (95% CI 87.9-88.3%) in the age- and sex-matched general population.In the general population, one in four patients with HF will not be hospitalized for worsening HF within a median follow-up of 1.7 years, yet they still have a poor 5-year prognosis. Patients admitted to hospital with worsening HF but not known with HF in primary care have the worst prognosis and management. Mitigating the prognostic burden of HF requires greater consistency across primary and secondary care in the identification, profiling, and treatment of patients.NCT02551016.

Improved prediction of early post-discharge death or rehospitalization after admission for acute heart failure is a major unmet need. We evaluated the value of biomarkers to predict either low or high risk for early post-discharge events.A total of 1653 patients enrolled in the PROTECT trial who were discharged alive and with available blood samples were included. Forty-seven biomarkers were serially evaluated in these patients. Measurement closest to discharge was used to evaluate the predictive value of biomarkers for low and high post-discharge risk. Patients were classified as 'low risk' if post-discharge 30-day risk of death or heart failure rehospitalization was5% while risk20% was used to define 'high risk'. Cut-off values that yielded a 95% negative predictive value and a 20% positive predictive value were identified for each biomarker. Partial area under the receiver operating characteristic curve (pAUC) in the high-sensitivity and high-specificity regions was calculated to compare low-risk and high-risk predictive values. Of patients analysed, 193 (11.7%) patients reached the 30-day death or heart failure rehospitalization outcome. We found marked differences between low-risk and high-risk predictors. Cardiac-specific troponin I was the strongest biomarker for low-risk prediction (pAUC = 0.552, 95% confidence interval 0.52-0.58) while endothelin-1 showed better performance for high-risk prediction (pAUC = 0.560, 95% confidence interval 0.53-0.59). Several biomarkers (individually and in combination) provided added predictive value, on top of a clinical model, in both low-risk and high-risk regions.Different biomarkers predicted low risk vs. high risk of early post-discharge death or heart failure readmission in patients hospitalized for acute heart failure.

Background Previous studies have shown that xanthine oxidase inhibitors (XOI) might improve outcome for patients with cardiovascular disease. However, more evidence is required. Methods and results We published a meta‐analysis of trials conducted before 2014 examining the effects of XOI on mortality in patients with cardiovascular disease. At least two further trials (N = 323 patients) have since been published. Accordingly, we repeated our analysis after a further search for randomized controlled trials of XOI in PubMed/MEDLINE, EMBASE, and Cochrane Databases. We identified eight relevant trials with 1031 patients. The average age of the patients was 61 years and 68% were men (one study did not report gender). There were 57 deaths in these eight trials, 26 in those assigned to XOI, and 31 in those assigned to the control. The updated meta‐analysis could not confirm a reduction in mortality for patients assigned to XOI compared with placebo (odds ratio 0.84) but 95% confidence intervals were wide (0.48–1.47). Conclusions This updated meta‐analysis does not suggest that XOI exert a large reduction in mortality but also cannot exclude the possibility of substantial harm or benefit.

Blood pressure (BP) control and reduction of urinary protein excretion using agents that block the renin-angiotensin aldosterone system are the mainstay of therapy for chronic kidney disease (CKD). Research has confirmed the benefits in mild CKD, but data on angiotensin-converting enzyme inhibitor (ACEi) or angiotensin receptor blocker (ARB) use in advanced CKD are lacking. In the STOP-ACEi trial, we aim to confirm preliminary findings which suggest that withdrawal of ACEi/ARB treatment can stabilize or even improve renal function in patients with advanced progressive CKD.The STOP-ACEi trial (trial registration: current controlled trials, ISRCTN62869767) is an investigator-led multicentre open-label, randomized controlled clinical trial of 410 participants with advanced (Stage 4 or 5) progressive CKD receiving ACEi, ARBs or both. Patients will be randomized in a 1:1 ratio to either discontinue ACEi, ARB or combination of both (experimental arm) or continue ACEi, ARB or combination of both (control arm). Patients will be followed up at 3 monthly intervals for 3 years. The primary outcome measure is eGFR at 3 years. Secondary outcome measures include the number of renal events, participant quality of life and physical functioning, hospitalization rates, BP and laboratory measures, including serum cystatin-C. Safety will be assessed to ensure that withdrawal of these treatments does not cause excess harm or increase mortality or cardiovascular events such as heart failure, myocardial infarction or stroke.The rationale and trial design are presented here. The results of this trial will show whether discontinuation of ACEi/ARBs can improve or stabilize renal function in patients with advanced progressive CKD. It will show whether this simple intervention can improve laboratory and clinical outcomes, including progression to end-stage renal disease, without causing an increase in cardiovascular events.

Introduction: Current US and European guidelines recommend that patients hospitalized with heart failure (HF) are followed up after discharge, but do not specify whether or not this should be with HF specialist services. We investigated referral patterns to specialist services amongst hospitals in England and Wales and assessed whether these differences were associated with 30-day mortality. Methods: We used data from the National Heart Failure Audit, which included 84647 HF patients from 176 hospitals. Vital status was obtained from the UK national death registry. Using hierarchical statistical models and instrumental variable analysis, we estimated whether different types of follow-up (cardiologist, HF nurse or geriatrician) were associated with 30-day mortality, adjusting for case mix. Results: At the hospital level, rates of referral to cardiologists for follow up varied from 4% to 94%, to HF nurses from 0% to 97% and to geriatricians from 0% to 65%. When heart failure patients were referred for follow-up to a heart failure nurse, to a geriatrician, or to a cardiologist, they were 15%, 15% and 47% less likely to die than patients who were not referred to these specialists (odds ratio [OR] = 0.85, p Conclusion: Referral at discharge to cardiology services for follow-up varies considerably amongst UK hospitals. At both an individual patient and at a hospital level, referral to cardiology for follow-up is a major determinant of 30-day mortality.

Chronic heart failure (CHF) is a global term for the physiological state in which cardiac output is insufficient to meet the needs of the body and lungs. While oxidative stress, defined as an excess production of reactive oxygen species relative to antioxidant defence, has been shown to play an important role in the pathophysiology of CHF. However, although high density lipoproteins (HDL) have important cardioprotective properties, inflammation and oxidative stress can induce dramatic changes, which negate their antiatherogenic properties. Thus, such impairment to HDL may provide an important link between inflammation and oxidative stress in the pathogenesis of CHF. This pilot study investigated the antiatherogenic properties of HDL in CHF. Ten control subjects (BNP100 nM). HDL 2 and HDL 3 were isolated from serum by rapid ultracentrifugation. SAA was measured by an ELISA procedure, paraoxonase-1 (PON-1) activity, hydroperoxide (HPO) and conjugated diene (CD) concentration were measured by spectrophotometric assays. Results: Compared to the control subjects, BNP was higher in the CHF subjects [50 (11) vs. 2439 (900) nM; p=0.015] and in HDL 2 and HDL 3 , SAA-related inflammation was increased, while the activity of the antioxidant enzyme PON-1 was decreased and CDs, one of the markers of lipid peroxidation, were increased (see table). Conclusion: This pilot study has shown that HDL displayed a proatherogenic phenotype in CHF subjects, which we suggest may be biologically relevant in the pathophysiology of CHF.

This study sought to examine the effect of statin therapy hospitalizations for heart failure (HFH) in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) trial.HFH is an important, frequently recurrent event. Conventional time-to-first event analyses do not take account repeat events. We used a number of statistical approaches to examine the effect of treatment on first and repeat HFH in the CORONA trial.In the CORONA trial, 5,011 patients ≥60 years of age with chronic New York Heart Association functional classes II to IV systolic heart failure resulting from ischemia were randomized to receive rosuvastatin or placebo. Poisson, Andersen-Gill, and negative binomial methods (NB) were used to analyze the effect of rosuvastatin on HFH, and the NB and a parametric joint frailty model (JF) were used to examine this effect while accounting for the competing risk of cardiovascular (CV) death. Rosuvastatin/placebo rate ratios were calculated, both unadjusted and adjusted.A total of 1,291 patients had 1 or more HFH (750 of these had a single HFH only), and there were a total of 2,408 HFHs. The hazard ratio for the conventional time-to-first event analysis for HFH was 0.91 (95% confidence interval [CI]: 0.82 to 1.02, p = 0.105). In contrast, the NB on repeat hospitalizations gave an unadjusted RR (RR) for HFH of 0.86 (95% CI: 0.75 to 0.99, p = 0.030), adjusted 0.82 (95% CI: 0.72 to 0.92, p = 0.001), and after including CV death as the last event, adjusted RR of 0.85 (95% CI: 0.77 to 0.94, p = 0.001). The JF gave an adjusted RR of 0.82 (95% CI: 0.73 to 0.92, p = 0.001). Similar results were found in analyses of all CV hospitalizations and all-cause hospitalizations.When repeat events were included, rosuvastatin was shown to reduce the risk of HFH by approximately 15% to 20%, equating to approximately 76 fewer admissions per 1,000 patients treated over a median 33 months of follow-up. Including repeat events could increase the ability to detect treatment effects in heart failure trials.

A Seawater Activated Power System (SWAPS) has most recently been tested for providing all electrical power for a US Navy Deep Water Detection System (DWADS). DWADS requires 40 kW bursts of power to produce acoustic pulses that are detected by submerged receivers whose signals are transmitted to and analyzed by ship or shore based operators.

Tethered buoys have long served as a common gateway for communications between underwater, terrestrial, and air assets. Although common, tethered buoys lack the versatility envisioned with an anchorless buoy that can closely maintain a station or waypoint as long as needed and be remotely commanded to move to another waypoint. Indeed, an untethered gateway buoy would have multiple uses in the defense, commercial and scientific sectors. The predominant challenge to develop an untethered buoy is generating enough energy for the buoy to maintain a station for months in open ocean currents. Falmouth Scientific, Inc. and its partners have developed an untethered, station-keeping, gateway buoy, named Gatekeeper, under an SBIR contract with the U.S. Navy. A spar-shape buoy, Gatekeeper inherently offers superior stability to meet the requirement for a persistent radio and satellite link A bail winch system for dropping and raising an acoustic transducer provides a robust underwater acoustic link. The primary energy and power source for the Gatekeeper is a 35 kilowatt-hour patent-pending Salt Water Activated Power System (SWAPS™), which provides at least 200 Watts of power. The Gatekeeper's SWAPS™ uses 55 pounds of an environmentally friendly metal alloy that reacts with saltwater to produce hydrogen for a fuel cell generator. SWAPS™ is an order of magnitude better than any battery technology in terms of mass, volume and cost for the same amount of energy. A solar panel array serves as a renewable energy source for the Gatekeeper system in order to preserve the SWAPS™ fuel, which is not renewable during deployment. A 2 kilowatt-hour battery is also used to store energy from the SWAPS™ and solar panels when the Gatekeeper is idling. Gatekeeper demonstrated excellent navigational and station-keeping capability at speeds up to 2 knots during a SBIR Phase Π sea trial in the Fall of 2008 and operated solely from the SWAPS™ and a solar array at speeds up to about 1.5 knots. Gatekeeper is projected to endure deployments that last several weeks with its configuration from the fall of 2008, which is a significant milestone. Improvements to Gatekeeper's endurance will be made in preparation for an at-sea endurance test that is planned for the early spring of 2010.

Ocean buoys often rely on batteries, solar cells, and wind and wave generated power to drive on-board instrumentation and communications equipment. Power demands are increasing as instrument requirements are added and deployment times extended. Un-tethered, station-keeping buoys also use much more energy and power for propulsion. Mil3, Inc has developed a superior Seawater Activated Power Source (SWAPSTM, patent-applied) which is more portable, safe, and economical for marine buoys and related applications. SWAPS utilizes a metal alloy reacting with saltwater to produce hydrogen as fuel for proton exchange membrane (PEM) fuel cells to produce electricity at efficiencies approaching 50%. With an energy density of 1.4 kWh/kg and scalability for power requirements of watts to kilowatts, SWAPS is lighter and less expensive than batteries, and can always produce 100% of its design output power. The only chemical by-product is a metal hydroxide which naturally occurs in seawater. SWAPS stores potential energy in its alloy fuel, provides power on-demand, is inherently self-regulating, and requires no moving parts or external control In contrast, batteries represent low energy density, excessive mass and volume and prohibitive costs for many applications. Bulky solar panels, and wind and wave driven generators do not provide energy storage and are dependent on factors such as time of day, weather conditions, tides, currents, and wind velocity. The best of these technologies may only produce 45% of its design power, which requires over-sizing and energy storage by batteries. Mil3 has proved the operation of an 80 W SWAPS unit on a prototype buoy representing a large meteorological buoy to be deployed for 6 months. Together with Falmouth Scientific Inc., Mil3 has also successfully demonstrated the use of a 35 kWh SWAPS unit to provide 180 W (220 W peak) to a station-keeping spar buoy built for the Navy. In sea states between 3 and 4, SWAPS consistently powered the buoy prop motor against currents greater than 1 knot, all instrumentation and radio telemetry, while additionally charging a Li-ion backup battery. The team is preparing a new SWAPS unit for providing all power for a 40 kW Navy acoustic pulsed power system.

PURPOSE To assess whether poor sleep quality carries prognostic significance for patients with suspected heart failure (HF). METHODS Data from patients referred to a HF clinic between July 2001 and October 2006 was analysed in a Cox Regression model to assess the prognostic significance of sleep quality. Patient responses for 3 questions addressing sleep quality (difficulty going to sleep, waking up in the night, and lack of refreshing sleep) were used to generate a sleep quality score (SQS) of 1 (none or minimal sleep impairment, N= 1054); 2 (mild to moderate sleep impairment, N= 908); or 3 (severe sleep impairment, N= 644). RESULTS Of 2606 patients, 59% were male. Median age was 72 yrs (Interquartile range (IQR) 65–78). There were 549 deaths during a median follow up of 37.5 months (IQR 26–46.4). Kaplan Meier survival curves showed that SQS 3 was associated with significantly worse prognosis (Figure 1 ), and this association persisted despite correction for age, sex, NYHA class, severity of LV systolic dysfunction, BMI, pulse pressure, lab parameters (sodium, creatinine, haemoglobin, NTproBNP, CRP and cholesterol), medication use (loop diuretics, ACE inhibitors, beta-blockers, statins and aldosterone antagonists) and comorbidities (diabetes, hypertension, AF, IHD, COPD and CVA)(Table 1 ). CONCLUSION Poor sleep quality is an independent prognostic marker in patients referred to a HF clinic. Cox Regression Analysis: Significant prognostic indicators

Objectives: To investigate the prognostic impact of right ventricular (RV) morphology in patients with mild and moderate heart failure. Methods: 80 normal subjects and 401 consecutive patients with left ventricular (LV) ejection fraction (EF)< 45%, on optimal treatment, underwent cardiac magnetic resonance imaging (C-MRI). The LV and the RV borders were detected from the short axis contiguous slices and drawn manually. Body surface area was used to index (I) the LV and RV mass (M) and volumes (V) measured at end-diastole (ED) and end-systole (ES). The indexed volumes were then used to calculate the LV and RV EF. RV dilatation was defined as mean RVESVI+2*SD in normal subjects. Results: 21 patients had incomplete data and excluded from the analysis. The median age for the remaining patients was 71 years and 86% were men. 77% had ischaemic heart disease and 78% had NYHA I/II breathlessness. The median LVEF was 33% and the RVEF 43%. 286 (75%) patients had normal and 94 (25%) dilated RV. Patients with RV dilation were more often male (92% vs. 84%, p=0.036), had lower systolic blood pressure (120mmHg vs. 129mmHg, p=0.003), and were more likely to have NYHA breathlessness III/IV (30% vs. 18%, p=0.006). Patients with normal RV had higher LVEF (34% vs. 31%, p=0.015), smaller LVEDVI (115ml/m 2 vs. 137ml/m 2 , p2 vs. 92ml/m 2 , p Conclusions: RV dilation is a common finding in patients with mild and moderate heart failure and is associated with worse prognosis.

Objectives: To assess procedural characteristics and adjudicated procedure-related (≤30 days) major adverse events among patients who underwent cardiac resynchronization therapy (CRT) implantation in the CARE-HF study. Background: The CARE-HF study shows that CRT improves symptoms and reduces morbidity and mortality in New York Heart Association (NYHA) class III/IV chronic heart failure (CHF) patients. However, safe and proper implantation of pacing systems remains key to effective CRT delivery. Methods: Generalized linear modeling was used to examine the relationships between 1 st implant success/failure and: NYHA class; beta-adrenergic blocker use; underlying ischemic versus non-ischemic heart disease; history of coronary artery bypass graft or valve surgery; left ventricular (LV) end-diastolic volume ≤ versus >300 cm 3 ; and, influence of the participating study-centers. Results: Implantation was attempted in 404/409 patients assigned to CRT, and in 65/404 patients assigned to medical therapy. Among these 469 patients, 450 (95.9%) received a successfully implanted and activated device. Complications occurred within 24 h in 47 patients (10.0%), mainly lead dislodgments (n=10, 2.1%) and coronary sinus dissection/perforation (n=10, 2.1%), and between 24 h and 30 days in 26 patients (5.5%), mainly lead dislodgment (n=13, 2.8%). Mean LV lead stimulation threshold was significantly higher than at the right atrium or right ventricle, though remained stable, delivering effective and reliable CRT. Implanting experience was the only predictor of procedural outcome. Conclusions: Transvenous CRT system implantation, using a CS lead designed for long-term LV pacing, was safe and reliable. As implanting centers become more experienced, this success rate is expected to increase further.

At the beginning of the 21st century, we are faced with a discrepancy between the favourable results produced by a series of large randomised controlled trials on heart failure and their poor implementation into clinical practice. (ACE-inhibition, beta-blockade, aldosterone antagonism). The organisation of care for patients with heart failure needs improvement. This is why the first large international survey was initiated to evaluate perception and practice of primary care physicians (PCPs) in the management of heart failure. In general, PCPs appeared well-informed about diagnostic steps and therapeutic interventions. In practice, most patients received appropriate diagnostic tests. The uptake of ACE inhibitors was high, but few patients were receiving recommended doses. Beta-blockers are currently underused but this situation may be changing rapidly. Though "IMPROVEMENT" might suggest we get it right fairly often, it does also indicate that the process is haphazard and that we could be much more efficient.

Gated blood-pool SPECT (GBPS) has several potential advantages over planar radionuclide ventriculography (PRNV), including the possibility of greater repeatability of left ventricular ejection fraction (LVEF) and the noninvasive calculation of left ventricular end-systolic volume and left ventricular end-diastolic volume (LVEDV). The aim of this study was to assess the repeatability of LVEF and LVEDV from GBPS and to compare LVEF with those from PRNV.Fifty patients underwent PRNV and GBPS, 23 of whom also had repeated studies in the same session. GPBS studies were processed using the Cedars Sinai Quantitative Blood-Pool SPECT (QBS) software that automatically calculates LVEF and LVEDV. Automatic processing with QBS was successful in 70% of the GBPS studies, with the remaining studies processed using the manual option in QBS. All PRNV studies were processed using a manual processing technique.Comparison of LVEF from PRNV and GBPS yielded a correlation coefficient of 0.80. Bland-Altman analysis demonstrated a mean difference of 0.74% +/- 7.62% (mean +/- SD) between LVEF from the 2 techniques. The 95% limits of agreement are therefore -14.50% to +15.98%. The correlation between repeated measurements was 0.87 for GBPS and 0.95 for PRNV. Bland-Altman analysis revealed poorer repeatability for GBPS (95% limits of agreement, -9.63% to +14.97% vs. -4.66% to +5.92%; P = 0.003). The mean LVEDV was 198 +/- 94 mL, with a mean difference of 9 +/- 47 mL between repeated measurements. The 95% limits of agreement are therefore -85 to +103 mL.GBPS provides a less repeatable measurement of LVEF than PRNV. Repeatability of LVEDV measurements from GBPS is poor.