Alcohol consumption and progression of heart failure in those at risk for or with pre-heart failure.

BACKGROUND: This study aims to understand the dose-response relationship between alcohol consumption, progression of left ventricular dysfunction (LVD) and/or symptomatic heart failure (HF) in an older European population at risk for HF (stage A) or with pre-HF (stage B). METHODS: This longitudinal, observational, secondary analysis of the St Vincent's Screening TO-Prevent Heart Failure (STOP-HF) follow-up study, excluded former alcohol drinkers and included patients with documented alcohol intake and echocardiography at baseline and follow up ≥18 months. It evaluated the relationship between alcohol intake and progression of LVD/symptomatic (stage C) HF in those at risk for or with pre-HF. RESULTS: Of 744 patients (mean age 66.5 [SD 9.8] years), 395 (53.1%) were female, and 260 (34.9%) had pre-HF at baseline. Overall, 201 (27.0%) patients reported no alcohol usage, 356 (47.8%) reported ≤70g/wk (low) alcohol intake and 187 (25.1%) reported >70g/wk (moderate-high). Over a median follow up of 5.44 [IQR 4.33;6.73] years, 84 (11.3%) patients had progression of LVD/symptomatic HF. Alcohol usage of >70g/wk was associated with an adjusted 4.9-fold (95% CI 1.7- 15.1, p<0.01) increased risk of HF progression amongst those with pre-HF at baseline. The adverse relationship remained significant when adjusting for age, sex, diabetes, hypertension, body mass index, as well as further models with baseline liver function and alcohol dehydrogenase 1B gene variant rs1229984 status. The association remained when excluding those with high (>140g) weekly alcohol intake. In patients at risk for HF there was no association of alcohol usage with progression of LVD/symptomatic HF. No protective associations of low alcohol usage (≤70g/wk) on progression of HF were found. CONCLUSION: Moderate to high alcohol (>70g/wk) usage appears to be associated with progression of LVD/symptomatic HF in those with pre-HF and we did not observe protective benefits of low alcohol usage.

A report from the Irish women in cardiology survey, exploring Europe's largest gender gap in cardiology.

Aims: In Ireland, 8% of public cardiology consultants are female; this is the lowest proportion in Europe. We sought to understand perceptions amongst Irish trainees and consultants regarding aspects of working in cardiology in order to identify areas that can be targeted to improve gender equality. Methods and Results: In September 2021, the Irish Cardiac Society distributed a questionnaire to trainees and consultants in the Republic and Northern Ireland. Ethical approval was obtained from the University College Dublin, Ireland. There were 94 respondents (50% male, 50% consultants) which equates to ∼30% of all trainees and consultants in all Ireland. Although females were more likely to be single, overall, they had additional child-care responsibilities compared with male counterparts. Despite 53% of the respondents preferring to work less than full time, 64% reported a perceived lack of support from their departments. Males were significantly more likely to go into procedural/high radiation sub-specialities. Bullying was reported by 53% of females. Almost 80% of females experienced sexism and 30% reported being overlooked for professional advancement based on their sex. Females also rated their career prospects lower than males. Key challenges for women were: sexism, maternity leave/child-care responsibilities, cardiology as a 'boys club' and lack of flexible training. There was interest from both males and females in a mentorship programme and support for women in leadership positions. Conclusion: Discrimination including sexism, bullying, and equal opportunity for professional advancement are key aspects that need to be addressed to improve gender balance in cardiology within Ireland and Northern Ireland.

Cardiac MRI e-prime predicts myocardial late gadolinium enhancement and diastolic dysfunction in hypertrophic cardiomyopathy.

BACKGROUND: Myocardial fibrosis leads to diastolic dysfunction in patients with hypertrophic cardiomyopathy (HCM). OBJECTIVES: To evaluate a manual method of measuring mitral annular relaxation velocity (termed cardiac MRI e') as a measure of diastolic dysfunction on routine cardiac MRI and its relationship with myocardial late-gadolinium enhancement (LGE) and feature tracking measures of diastolic dysfunction in patients with HCM. METHODS: CMR e', feature tracking measures of diastolic function, left atrial, left ventricular (LV) parameters and LGE were retrospectively measured in 75 patients with HCM (mean age, 54.7 years ± 15.3, 54 men). Multivariate regression and partial Spearman correlations were performed. RESULTS: Cardiac MRI e' measures correlated with LGE (r = 0.49, P < 0.001) and multiple feature tracking measures of diastolic function, adjusted for patient demographics, left atrial and left ventricular parameters. Cardiac MRI e' measures were independently predictive of LGE ≥ 10% (mean total cardiac MRI e': LGE < 10% vs LGE ≥ 10% was 3.5 cm/s vs. 1.7 cm/s, P < 0.001). Superior CMR e' had an AUC of 0.79 [95%CI 0.66-0.92, P < 0.0001]) in predicting patients with LGE ≥ 10% and a cutoff of 1.7 cm/s resulted in a sensitivity and specificity of 81.0% and 78.0% respectively. CONCLUSION: Cardiac MRI e' is a manual measure of LV diastolic dysfunction acquired on routine cardiac MRI without specialized software and is an independent predictor of LGE ≥ 10% and diastolic dysfunction in HCM.

A Machine Learning Approach for Chronic Heart Failure Diagnosis.

The aim of this study was to address chronic heart failure (HF) diagnosis with the application of machine learning (ML) approaches. In the present study, we simulated the procedure that is followed in clinical practice, as the models we built are based on various combinations of feature categories, e.g., clinical features, echocardiogram, and laboratory findings. We also investigated the incremental value of each feature type. The total number of subjects utilized was 422. An ML approach is proposed, comprising of feature selection, handling class imbalance, and classification steps. The results for HF diagnosis were quite satisfactory with a high accuracy (91.23%), sensitivity (93.83%), and specificity (89.62%) when features from all categories were utilized. The results remained quite high, even in cases where single feature types were employed.

A pragmatic parallel group implementation study of a prehospital-activated ECPR protocol for refractory out-of-hospital cardiac arrest.

OBJECTIVES: Extracorporeal membrane oxygenation within CPR (ECPR) may improve survival among patients with refractory out-of-hospital cardiac arrest (OHCA). We evaluated outcomes after incorporating ECPR into a conventional resuscitation system. METHODS: We introduced a prehospital-activated ECPR protocol for select refractory OHCAs into one of four metropolitan regions in British Columbia. We prospectively identified ECPR-eligible patients in both the ECPR region and the three other regions to serve as the control group. We compared the proportion with favorable neurological outcomes at hospital discharge (cerebral performance category ≤2) and used logistic regression to estimate the association with treatment region. RESULTS: The study was terminated prematurely due to changes in hospital protocols and COVID-19. In the ECPR region, 15/58 (25.9%) patients had favourable neurological outcomes owing to conventional resuscitation and 2/58 (3.4%) owing to ECPR, for a total of 17/58 (29.3%). In the control regions, 67/250 (26.8%) patients had a favourable outcome owing to conventional resuscitation, for a between-group difference of 2.5% (95% CI -10 to 15%). We did not detect a statistically significant association between treatment region and outcomes. CONCLUSION: In this prematurely-terminated study of ECPR for refractory OHCA, we did not detect an association between a regional ECPR protocol and neurologically favorable outcomes. However, our data suggests that outcomes owing to conventional resuscitation were similar, with the potential for additional survivors due to ECPR therapies.

A qualitative exploratory case series of patient and family experiences with ECPR for out-of-hospital cardiac arrest.

OBJECTIVE: There is currently no existing data examining the opinions of patients and families after treatment with extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA). We sought to interview family members and patients to learn from their experiences and satisfaction with treatment. METHODS: We contacted family members and survivors for all cases treated with ECPR for refractory OHCA at St. Paul's Hospital between January 2014 and July 2018. We performed semi-structured interviews with participants, specifically within the topics of: information sharing (including impressions of an ECPR informational pamphlet), prognostication, organ donation, and perceived value of ECPR. Due to low participant enrolment, we described all interviews in a narrative approach. RESULTS: Within the study period, there were 23 OHCAs treated with ECPR; two survivors and three family members agreed to participate. Participants were satisfied with the treatment provided, including information sharing and prognostication. There were mixed opinions about the best method of information-sharing (verbal vs written), as well as the timing of organ donation conversations. All participants believed ECPR for OHCA to be of high value. CONCLUSION: Patient's conveyed satisfaction with ECPR treatment, with mixed views on the best information sharing strategy. Further study is needed to define the optimal methods and timing for discussions of organ donation, especially for treatments of with a relatively low likelihood success.

Multiplexed measurement of candidate blood protein biomarkers of heart failure.

AIMS: There is a critical need for better biomarkers so that heart failure can be diagnosed at an earlier stage and with greater accuracy. The purpose of this study was to design a robust mass spectrometry (MS)-based assay for the simultaneous measurement of a panel of 35 candidate protein biomarkers of heart failure, in blood. The overall aim was to evaluate the potential clinical utility of this biomarker panel for prediction of heart failure in a cohort of 500 patients. METHODS AND RESULTS: Multiple reaction monitoring (MRM) MS assays were designed with Skyline and Spectrum Mill PeptideSelector software and developed using nanoflow reverse phase C18 chromatographic Chip Cube-based separation, coupled to a 6460 triple quadrupole mass spectrometer. Optimized MRM assays were applied, in a sample-blinded manner, to serum samples from a cohort of 500 patients with heart failure and non-heart failure (non-HF) controls who had cardiovascular risk factors. Both heart failure with reduced ejection fraction (HFrEF) patients and heart failure with preserved ejection fraction (HFpEF) patients were included in the study. Peptides for the Apolipoprotein AI (APOA1) protein were the most significantly differentially expressed between non-HF and heart failure patients (P = 0.013 and P = 0.046). Four proteins were significantly differentially expressed between non-HF and the specific subtypes of HF (HFrEF and HFpEF); Leucine-rich-alpha-2-glycoprotein (LRG1, P < 0.001), zinc-alpha-2-glycoprotein (P = 0.005), serum paraoxanse/arylesterase (P = 0.013), and APOA1 (P = 0.038). A statistical model found that combined measurements of the candidate biomarkers in addition to BNP were capable of correctly predicting heart failure with 83.17% accuracy and an area under the curve (AUC) of 0.90. This was a notable improvement on predictive capacity of BNP measurements alone, which achieved 77.1% accuracy and an AUC of 0.86 (P = 0.005). The protein peptides for LRG1, which contributed most significantly to model performance, were significantly associated with future new onset HF in the non-HF cohort [Peptide 1: odds ratio (OR) 2.345 95% confidence interval (CI) (1.456-3.775) P = 0.000; peptide 2: OR 2.264 95% CI (1.422-3.605), P = 0.001]. CONCLUSIONS: This study has highlighted a number of promising candidate biomarkers for (i) diagnosis of heart failure and subtypes of heart failure and (ii) prediction of future new onset heart failure in patients with cardiovascular risk factors. Furthermore, this study demonstrates that multiplexed measurement of a combined biomarker signature that includes BNP is a more accurate predictor of heart failure than BNP alone.

Biomarker profiling for risk of future heart failure (HFpEF) development.

BACKGROUND: The purpose of this study was to investigate the utility of BNP, hsTroponin-I, interleukin-6, sST2, and galectin-3 in predicting the future development of new onset heart failure with preserved ejection fraction (HFpEF) in asymptomatic patients at-risk for HF. METHODS: This is a retrospective analysis of the longitudinal STOP-HF study of thirty patients who developed HFpEF matched to a cohort that did not develop HFpEF (n = 60) over a similar time period. Biomarker candidates were quantified at two time points prior to initial HFpEF diagnosis. RESULTS: HsTroponin-I and BNP at baseline and follow-up were statistically significant predictors of future new onset HFpEF, as was galectin-3 at follow-up and concentration change over time. Interleukin-6 and sST2 were not predictive of future development of new onset HFpEF in this study. Unadjusted biomarker combinations of hsTroponin-I, BNP, and galectin-3 could significantly predict future HFpEF using both baseline (AUC 0.82 [0.73,0.92]) and follow-up data (AUC 0.86 [0.79,0.94]). A relative-risk matrix was developed to categorize the relative-risk of new onset of HFpEF based on biomarker threshold levels. CONCLUSION: We provided evidence for the utility of BNP, hsTroponin-I, and Galectin-3 in the prediction of future HFpEF in asymptomatic event-free populations with cardiovascular disease risk factors.

The effect of spironolactone on cardiovascular function and markers of fibrosis in people at increased risk of developing heart failure: the heart 'OMics' in AGEing (HOMAGE) randomized clinical trial.

AIMS: To investigate the effects of spironolactone on fibrosis and cardiac function in people at increased risk of developing heart failure. METHODS AND RESULTS: Randomized, open-label, blinded-endpoint trial comparing spironolactone (50 mg/day) or control for up to 9 months in people with, or at high risk of, coronary disease and raised plasma B-type natriuretic peptides. The primary endpoint was the interaction between baseline serum galectin-3 and changes in serum procollagen type-III N-terminal pro-peptide (PIIINP) in participants assigned to spironolactone or control. Procollagen type-I C-terminal pro-peptide (PICP) and collagen type-1 C-terminal telopeptide (CITP), reflecting synthesis and degradation of type-I collagen, were also measured. In 527 participants (median age 73 years, 26% women), changes in PIIINP were similar for spironolactone and control [mean difference (mdiff): -0.15; 95% confidence interval (CI) -0.44 to 0.15 µg/L; P = 0.32] but those receiving spironolactone had greater reductions in PICP (mdiff: -8.1; 95% CI -11.9 to -4.3 µg/L; P < 0.0001) and PICP/CITP ratio (mdiff: -2.9; 95% CI -4.3 to -1.5; <0.0001). No interactions with serum galectin were observed. Systolic blood pressure (mdiff: -10; 95% CI -13 to -7 mmHg; P < 0.0001), left atrial volume (mdiff: -1; 95% CI -2 to 0 mL/m2; P = 0.010), and NT-proBNP (mdiff: -57; 95% CI -81 to -33 ng/L; P < 0.0001) were reduced in those assigned spironolactone. CONCLUSIONS: Galectin-3 did not identify greater reductions in serum concentrations of collagen biomarkers in response to spironolactone. However, spironolactone may influence type-I collagen metabolism. Whether spironolactone can delay or prevent progression to symptomatic heart failure should be investigated.

Atrial Tissue Pro-Fibrotic M2 Macrophage Marker CD163+, Gene Expression of Procollagen and B-Type Natriuretic Peptide.

Background Atrial tissue fibrosis is linked to inflammatory cells, yet is incompletely understood. A growing body of literature associates peripheral blood levels of the antifibrotic hormone BNP (B-type natriuretic peptide) with atrial fibrillation (AF). We investigated the relationship between pro-fibrotic tissue M2 macrophage marker Cluster of Differentiation (CD)163+, atrial procollagen expression, and BNP gene expression in patients with and without AF. Methods and Results In a cross-sectional study design, right atrial tissue was procured from 37 consecutive, consenting, stable patients without heart failure or left ventricular systolic dysfunction, of whom 10 had AF and 27 were non-AF controls. Samples were analyzed for BNP and fibro-inflammatory gene expression, as well as fibrosis and CD163+. Primary analyses showed strong correlations (all P<0.008) between M2 macrophage CD163+ staining, procollagen gene expression, and myocardial BNP gene expression across the entire cohort. In secondary analyses without multiplicity adjustments, AF patients had greater left atrial volume index, more valve disease, higher serum BNP, and altered collagen turnover markers versus controls (all P<0.05). AF patients also showed higher atrial tissue M2 macrophage CD163+, collagen volume fraction, gene expression of procollagen 1 and 3, as well as reduced expression of the BNP clearance receptor NPRC (all P<0.05). Atrial procollagen 3 gene expression was correlated with fibrosis and BNP gene expression was correlated with serum BNP. Conclusions Elevated atrial tissue pro-fibrotic M2 macrophage CD163+ is associated with increased myocardial gene expression of procollagen and anti-fibrotic BNP and is higher in patients with AF. More work on modulation of BNP signaling for treatment and prevention of AF may be warranted.

Comparison of longitudinal change in sST2 vs BNP to predict major adverse cardiovascular events in asymptomatic patients in the community.

Biomarker-based preventative and monitoring strategies are increasingly used for risk stratification in cardiovascular (CV) disease. The aim of this study was to investigate the utility of longitudinal change in B-type natriuretic peptide (BNP) and sST2 concentrations for predicting incident major adverse CV events (MACE) (heart failure, myocardial infarction, arrhythmia, stroke/transient ischaemic attack and CV death) in asymptomatic community-based patients with risk factors but without prevalent MACE at enrolment. The study population consisted of 282 patients selected from the longitudinal STOP-HF study of asymptomatic patients with risk factors for development of MACE. Fifty-two of these patients developed a MACE. The study was run in two phases comprising of an initial investigative cohort (n = 195), and a subsequent 2:1 (No MACE: MACE) propensity matched verification cohort (n = 87). BNP and sST2 were quantified in all patients at two time points a median of 2.5 years apart. Results highlighted that longitudinal change in sST2 was a statistically significant predictor of incident MACE, (AUC 0.60). A one-unit increment in sST2 change from baseline to follow up corresponded to approximately 7.99% increase in the rate of one or more incident MACE, independent of the baseline or follow-up concentration. In contrast, longitudinal change value of BNP was not associated with MACE. In conclusion, longitudinal change in sST2 but not BNP was associated with incident MACE in asymptomatic, initially event-free patients in the community. Further work is required to evaluate the clinical utility of change in sST2 in risk prediction and event monitoring in this setting.

Natriuretic peptide-guided treatment for the prevention of cardiovascular events in patients without heart failure.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of morbidity and mortality globally. Early intervention for those with high cardiovascular risk is crucial in improving patient outcomes. Traditional prevention strategies for CVD have focused on conventional risk factors, such as overweight, dyslipidaemia, diabetes, and hypertension, which may reflect the potential for cardiovascular insult. Natriuretic peptides (NPs), including B-type natriuretic peptide (BNP) and N-terminal pro B-type natriuretic peptide (NT-proBNP), are well-established biomarkers for the detection and diagnostic evaluation of heart failure. They are of interest for CVD prevention because they are secreted by the heart as a protective response to cardiovascular stress, strain, and damage. Therefore, measuring NP levels in patients without heart failure may be valuable for risk stratification, to identify those at highest risk of CVD who would benefit most from intensive risk reduction measures. OBJECTIVES: To assess the effects of natriuretic peptide (NP)-guided treatment for people with cardiovascular risk factors and without heart failure. SEARCH METHODS: Searches of the following bibliographic databases were conducted up to 9 July 2019: CENTRAL, MEDLINE, Embase, and Web of Science. Three clinical trial registries were also searched in July 2019. SELECTION CRITERIA: We included randomised controlled trials enrolling adults with one or more cardiovascular risk factors and without heart failure, which compared NP-based screening and subsequent NP-guided treatment versus standard care in all settings (i.e. community, hospital). DATA COLLECTION AND ANALYSIS: Two review authors independently screened titles and abstracts and selected studies for inclusion, extracted data, and evaluated risk of bias. Risk ratios (RRs) were calculated for dichotomous data, and mean differences (MDs) with 95% confidence intervals (CIs) were calculated for continuous data. We contacted trial authors to obtain missing data and to verify crucial study characteristics. Using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, two review authors independently assessed the quality of the evidence and GRADE profiler (GRADEPRO) was used to import data from Review Manager to create a 'Summary of findings' table. MAIN RESULTS: We included two randomised controlled trials (three reports) with 1674 participants, with mean age between 64.1 and 67.8 years. Follow-up ranged from 2 years to mean 4.3 years.For primary outcome measures, effect estimates from a single study showed uncertainty for the effect of NP-guided treatment on cardiovascular mortality in patients with cardiovascular risk factors and without heart failure (RR 0.33, 95% CI 0.04 to 3.17; 1 study; 300 participants; low-quality evidence). Pooled analysis demonstrated that in comparison to standard care, NP-guided treatment probably reduces the risk of cardiovascular hospitalisation (RR 0.52, 95% CI 0.40 to 0.68; 2 studies; 1674 participants; moderate-quality evidence). This corresponds to a risk of 163 per 1000 in the control group and 85 (95% CI 65 to 111) per 1000 in the NP-guided treatment group.When secondary outcome measures were evaluated, evidence from a pooled analysis showed uncertainty for the effect of NP-guided treatment on all-cause mortality (RR 0.90, 95% CI 0.60 to 1.35; 2 studies; 1354 participants; low-quality evidence). Pooled analysis indicates that NP-guided treatment probably reduces the risk of all-cause hospitalisation (RR 0.83, 95% CI 0.75 to 0.92; 2 studies; 1354 participants; moderate-quality evidence). This corresponds to a risk of 601 per 1000 in the control group and 499 (95% CI 457 to 553) per 1000 in the NP-guided treatment group. The effect estimate from a single study indicates that NP-guided treatment reduced the risk of ventricular dysfunction (RR 0.61, 95% CI 0.41 to 0.91; 1374 participants; high-quality evidence). The risk in this study's control group was 87 per 1000, compared with 53 (95% CI 36 to 79) per 1000 with NP-guided treatment. Results from the same study show that NP-guided treatment does not affect change in NP level at the end of follow-up, relative to standard care (MD -4.06 pg/mL, 95% CI -15.07 to 6.95; 1 study; 1374 participants; moderate-quality evidence). AUTHORS' CONCLUSIONS: This review shows that NP-guided treatment is likely to reduce ventricular dysfunction and cardiovascular and all-cause hospitalisation for patients who have cardiovascular risk factors and who do not have heart failure. Effects on mortality and natriuretic peptide levels are less certain. Neither of the included studies were powered to evaluate mortality. Available evidence shows uncertainty regarding the effects of NP-guided treatment on both cardiovascular mortality and all-cause mortality; very low event numbers resulted in a high degree of imprecision in these effect estimates. Evidence also shows that NP-guided treatment may not affect NP level at the end of follow-up.As both trials included in our review were pragmatic studies, non-blinding of patients and practices may have biased results towards a finding of equivalence. Further studies with more adequately powered sample sizes and longer duration of follow-up are required to evaluate the effect of NP-guided treatment on mortality. As two trials are ongoing, one of which is a large multi-centre trial, it is hoped that future iterations of this review will benefit from larger sample sizes across a wider geographical area.

A comprehensive regional clinical and educational ECPR protocol decreases time to ECMO in patients with refractory out-of-hospital cardiac arrest.

OBJECTIVE: Extracorporeal membrane oxygenation within CPR (ECPR) may improve survival for refractory out-of-hospital cardiac arrest (OHCA). We developed a prehospital, emergency department (ED), and hospital-based clinical and educational protocol to improve the key variable of time-to-ECPR (TTE). METHODS: In a single urban health region we involved key prehospital, clinical, and administrative stakeholders over a 2-year period, to develop a regional ECPR program with destination to a single urban tertiary care hospital. We developed clear and reproducible inclusion criteria and processes, including measures of program efficiency. We conducted seminars and teaching modules to paramedics and hospital-based clinicians including monthly simulator sessions, and performed detailed reviews of each treated case in the form of report cards. In this before-and-after study we compared patients with ECPR attempted prior to, and after, protocol implementation. The primary outcome was TTE, defined as the time of initial professional CPR to establishment of extracorporeal circulation. We compared the median TTE for patients in the two groups using the Wilcoxon signed rank test. RESULTS: Four patients were identified prior to the protocol and managed in an ad hoc basis; for nine patients the protocol was utilized. Overall favourable neurological outcomes among ECPR-treated patients were 27%. The median TTE was 136 minutes (IQR 98 - 196) in the pre-protocol group, and 60 minutes (IQR 49 - 81) minutes in the protocol group (p=0.0165). CONCLUSION: An organized clinical and educational protocol to initiate ECPR for patients with OHCA is feasible and significantly reduces the key benchmark of time-to-ECPR flows.

Evolving Use of Natriuretic Peptides as Part of Strategies for Heart Failure Prevention.

BACKGROUND: Heart failure (HF) remains one of the major cardiovascular challenges to the Western world. Once established, HF is characterized by compromised life expectancy and quality of life with considerable dependence on hospital care for episodic clinical deterioration. Much is understood about the risk factors that predispose to the development of HF. With such a broad range of factors, it is clear that there is a large population at risk, potentially in excess of 25% of the adult population. Therein lies the major challenge at the outset of our efforts to prevent HF. With such a large population at risk, how do we develop an effective prevention strategy? CONTENT: HF prevention requires a multimodal approach. In this review, we focus primarily on the role of natriuretic peptide (NP) as a tool in a prevention strategy. SUMMARY: Prevention of HF is a major public health challenge, underlined by the concerning epidemiological trends, the associated costs, and the continued difficulty to find effective therapies for the growing number of patients with preserved systolic function HF. Population-based approaches focusing on lifestyle and risk factor control have made some impact but not to a satisfactory level and also tend to result in a uniform approach across a population with different risk profiles. Individualizing risk is therefore required, with emerging data indicating that NP-guided risk stratification and intervention can reduce downstream incident HF and other cardiovascular events.

Influence of diabetes on natriuretic peptide thresholds in screening for Stage B heart failure.

CONTEXT: Natriuretic peptide (NP) has been shown to be an effective screening tool to identify patients with Stage B heart failure and to have clinical value in preventing heart failure progression. The impact of associated metabolic confounders on the screening utility of NP needs clarification. OBJECTIVE: To assess the impact of diabetes mellitus (DM) on NP screening for asymptomatic Stage B heart failure. MATERIALS AND METHODS: The study population consisted of 1368 asymptomatic patients with cardiovascular risk factors recruited from general practice as part of the STOP-HF trial. B-type NP (BNP) was quantified at point-of-care. RESULTS: BNP was found to be as accurate for detecting Stage B heart failure in DM patients compared to non-DM patients (AUC 0.75 [0.71,0.78] and 0.77 [0.72,0.82], respectively). However, different BNP thresholds are required to achieve the same level of diagnostic sensitivity in DM compared with non-DM patients. To achieve 80% sensitivity a difference of 5-ng/L lower is required for patients with DM. CONCLUSION: Although a significantly different BNP threshold is detected for patients with DM, the BNP concentration difference is small and unlikely to warrant a clinically different diagnostic threshold.

Epigenetic Therapy for the Treatment of Hypertension-Induced Cardiac Hypertrophy and Fibrosis.

BACKGROUND: The development of heart failure is associated with changes in the size, shape, and structure of the heart that has a negative impact on cardiac function. These pathological changes involve excessive extracellular matrix deposition within the myocardial interstitium and myocyte hypertrophy. Alterations in fibroblast phenotype and myocyte activity are associated with reprogramming of gene transcriptional profiles that likely requires epigenetic alterations in chromatin structure. The aim of our work was to investigate the potential of a currently licensed anticancer epigenetic modifier as a treatment option for cardiac diseases associated with hypertension-induced cardiac hypertrophy and fibrosis. METHODS AND RESULTS: The effects of DNA methylation inhibition with 5-azacytidine (5-aza) were examined in a human primary fibroblast cell line and in a spontaneously hypertensive rat (SHR) model. The results from this work allude to novel in vivo antifibrotic and antihypertrophic actions of 5-aza. Administration of the DNA methylation inhibitor significantly improved several echocardiographic parameters associated with hypertrophy and diastolic dysfunction. Myocardial collagen levels and myocyte size were reduced in 5-aza-treated SHRs. These findings are supported by beneficial in vitro effects in cardiac fibroblasts. Collagen I, collagen III, and α-smooth muscle actin were reduced in a human ventricular cardiac fibroblast cell line treated with 5-aza. CONCLUSION: These findings suggest a role for epigenetic modifications in contributing to the profibrotic and hypertrophic changes evident during disease progression. Therapeutic intervention with 5-aza demonstrated favorable effects highlighting the potential use of this epigenetic modifier as a treatment option for cardiac pathologies associated with hypertrophy and fibrosis.

Serum Amyloid P-Component Prevents Cardiac Remodeling in Hypertensive Heart Disease.

The potential for serum amyloid P-component (SAP) to prevent cardiac remodeling and identify worsening diastolic dysfunction (DD) was investigated. The anti-fibrotic potential of SAP was tested in an animal model of hypertensive heart disease (spontaneously hypertensive rats treated with SAP [SHR - SAP] × 12 weeks). Biomarker analysis included a prospective study of 60 patients with asymptomatic progressive DD. Compared with vehicle-treated Wistar-Kyoto rats (WKY-V), the vehicle-treated SHRs (SHR-V) exhibited significant increases in left ventricular mass, perivascular collagen, cardiomyocyte size, and macrophage infiltration. SAP administration was associated with significantly lower left ventricular mass (p < 0.01), perivascular collagen (p < 0.01), and cardiomyocyte size (p < 0.01). Macrophage infiltration was significantly attenuated in the SHR-SAP group. Biomarker analysis showed significant decreases in SAP concentration over time in patients with progressive DD (p < 0.05). Our results indicate that SAP prevents cardiac remodeling by inhibiting recruitment of pro-fibrotic macrophages and that depleted SAP levels identify patients with advancing DD suggesting a role for SAP therapy.