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Aims: Diabetes is a potent risk factor for death and heart failure (HF) hospitalization following myocardial infarction (MI). Whether diabetes modifies the relationship between left ventricular ejection fraction (LVEF) and outcomes in the post-MI population is unknown., Methods and Results: The Valsartan in Acute Myocardial Infarction trial (VALIANT) enrolled 14 703 patients with acute MI complicated by HF, systolic dysfunction, or both. We compared the risk of death, HF hospitalization, and/or recurrent MI among patients with and without diabetes using Cox proportional hazards models. To assess the relationship between diabetes, LVEF and outcomes, we assessed the relative influence of baseline LVEF on outcomes in diabetic and non-diabetic patients. Totally, 11 325 subjects (3095 diabetics) with site-reported LVEF and known diabetes status were included. At any given LVEF, diabetes was associated with a higher risk of all-cause mortality [adjusted hazard ratio (HR) 1.37, 95% CI 1.25-1.51], death or HF hospitalization (adjusted HR 1.42, 95% CI 1.31-1.51), and death or recurrent MI (adjusted HR 1.36, 95% CI 1.24-1.48). Diabetes modified the relationship between LVEF and death or HF hospitalization (P for interaction = 0.0109), such that the association between diabetes and increased risk was greater in magnitude at higher LVEF. No interaction was noted between diabetes and LVEF on risk of all-cause mortality or death or recurrent MI., Conclusion: Diabetes is associated with a higher risk of death or HF hospitalization across the spectrum of LVEF in high-risk post-MI patients. The magnitude of reduction in risk of death or HF hospitalization associated with increasing LVEF is significantly attenuated among patients with diabetes when compared to patients without diabetes.

Aims: Biologically active adrenomedullin (bio-ADM) is a promising marker of residual congestion. The STRONG-HF trial showed that high-intensity care (HIC) of guideline-directed medical therapy (GDMT) improved congestion and clinical outcomes in heart failure (HF) patients. The association between bio-ADM, decongestion, outcomes and the effect size of HIC of GDMT remains to be elucidated., Methods and Results: We measured plasma bio-ADM concentrations in 1005 patients within 2 days prior to anticipated discharge (baseline) and 90 days later. Bio-ADM correlated with most signs of congestion, with the exception of rales. Changes in bio-ADM were strongly correlated with change in congestion status from baseline to day 90 (gamma -0.24; p = 0.0001). Patients in the highest tertile of baseline bio-ADM concentrations were at greater risk than patients in the lowest tertile for the primary outcome of 180-day all-cause mortality or HF rehospitalization (hazard ratio [HR] 2.14, 95% confidence interval [CI] 1.42-3.22) and 180-day HF rehospitalization (HR 2.33, 95% CI 1.38-3.94). Areas under the receiver-operating characteristic curves were 0.5977 (95% CI 0.5561-0.6393), 0.5800 (95% CI 0.5356-0.6243), and 0.6159 (95% CI 0.5711-0.6607) for bio-ADM, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and their combination, respectively, suggesting that both bio-ADM and NT-proBNP provided similarly modest discrimination for this outcome. A trend towards better discrimination by combined bio-ADM and NT-proBNP than NT-proBNP alone was found (p = 0.059). HIC improved the primary outcome, irrespective of baseline bio-ADM concentration (interaction p = 0.37). In contrast to NT-proBNP, the 90-day change in bio-ADM did not differ significantly between HIC and usual care., Conclusions: Bio-ADM is a marker of congestion and predicts congestion at 3 months after a HF hospitalization. Higher bio-ADM was modestly associated with a higher risk of death and early hospital readmission and may have added value when combined with NT-proBNP., (© 2024 The Author(s). European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Aim: Acute decompensated heart failure (ADHF) is the leading cause of cardiovascular hospitalizations in the United States. Detecting B‐lines through lung ultrasound (LUS) can enhance clinicians' prognostic and diagnostic capabilities. Artificial intelligence/machine learning (AI/ML)‐based automated guidance systems may allow novice users to apply LUS to clinical care. We investigated whether an AI/ML automated LUS congestion score correlates with expert's interpretations of B‐line quantification from an external patient dataset. Methods and results: This was a secondary analysis from the BLUSHED‐AHF study which investigated the effect of LUS‐guided therapy on patients with ADHF. In BLUSHED‐AHF, LUS was performed and B‐lines were quantified by ultrasound operators. Two experts then separately quantified the number of B‐lines per ultrasound video clip recorded. Here, an AI/ML‐based lung congestion score (LCS) was calculated for all LUS clips from BLUSHED‐AHF. Spearman correlation was computed between LCS and counts from each of the original three raters. A total of 3858 LUS clips were analysed on 130 patients. The LCS demonstrated good agreement with the two experts' B‐line quantification score (r = 0.894, 0.882). Both experts' B‐line quantification scores had significantly better agreement with the LCS than they did with the ultrasound operator's score (p < 0.005, p < 0.001). Conclusion: Artificial intelligence/machine learning‐based LCS correlated with expert‐level B‐line quantification. Future studies are needed to determine whether automated tools may assist novice users in LUS interpretation. [ABSTRACT FROM AUTHOR]

Aims: We examined the effectiveness of a novel cardiopulmonary management wearable sensor (worn for less than 5 mins) at measuring congestion and correlated the device findings with established clinical measures of congestion., Methods and Results: We enrolled three cohorts of patients: (1) patients with heart failure (HF) receiving intravenous diuretics in hospital; (2) patients established on haemodialysis, and (3) HF patients undergoing right heart catheterization (RHC). The primary outcomes in the respective cohorts were a Spearman correlation between (1) change in weight and change in thoracic impedance (TI) (from enrolment, 24 h after admission to discharge) in patients hospitalized for HF; (2) lung ultrasound B-lines and volume removed during dialysis with device measured TI, and (3) pulmonary capillary wedge pressure (PCWP) and sub-acoustic diastolic, third heart sound (S3) in the patients undergoing RHC. A total of 66 patients were enrolled. In HF patients (n = 25), change in weight was correlated with both change in device TI (Spearman correlation [r sp ] = -0.64, p = 0.002) and change in device S3 (r sp  = -0.53, p = 0.014). In the haemodialysis cohort (n = 21), B-lines and TI were strongly correlated before (r sp  = -0.71, p < 0.001) and after (r sp  = -0.77, p < 0.001) dialysis. Volume of fluid removed by dialysis was correlated with change in device TI (r sp  = 0.49, p = 0.024). In the RHC cohort (n = 20), PCWP measured at one time point and device S3 were not significantly correlated (r sp  = 0.230, p = 0.204). There were no device-related adverse events., Conclusions: A non-invasive device was able to detect changes in congestion in patients with HF receiving decongestion therapy and patients having fluid removed at haemodialysis. The cardiopulmonary management device, which measures multiple parameters, is a potentially useful tool to monitor patients with HF to prevent hospitalizations., (© 2024 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Episodes of worsening symptoms and signs characterize the clinical course of patients with chronic heart failure (HF). These events are associated with poorer quality of life, increased risks of hospitalization and death and are a major burden on healthcare resources. They usually require diuretic therapy, either administered intravenously or by escalation of oral doses or with combinations of different diuretic classes. Additional treatments may also have a major role, including initiation of guideline‐recommended medical therapy (GRMT). Hospital admission is often necessary but treatment in the emergency service or in outpatient clinics or by primary care physicians has become increasingly used. Prevention of first and recurring episodes of worsening HF is an essential component of HF treatment and this may be achieved through early and rapid administration of GRMT. The aim of the present clinical consensus statement by the Heart Failure Association of the European Society of Cardiology is to provide an update on the definition, clinical characteristics, management and prevention of worsening HF in clinical practice. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to examine the association between patient‐reported symptoms and the extent of pulmonary congestion in acute heart failure (AHF). Methods and results: In this prospective, observational study, patient‐reported symptoms were assessed at baseline using the Kansas City Cardiomyopathy Questionnaire total symptom score (KCCQ‐TSS) (range 0–100; 0 worst) in patients hospitalized for AHF. In a subset, patient‐reported dyspnoea at rest and on exertion was examined (range 0–10; 10 worst) at baseline. In addition, 4‐zone lung ultrasound (LUS) was performed at baseline at the time of echocardiography. B‐lines were quantified offline, blinded to clinical findings, by a core laboratory. Chest X‐ray (CXR) and physical examination findings were collected from the medical records. Among 322 patients (mean age 72, 60% men, mean left ventricular ejection fraction 39%) with AHF, the median KCCQ‐TSS score was 33 (interquartile range 18–48). Worse KCCQ‐TSS was associated with worse New York Heart Association class, dyspnoea at rest and on exertion, and peripheral oedema (p trend <0.001 for all). However, KCCQ‐TSS was not associated with the extent of pulmonary congestion, as assessed by the number of B‐lines on LUS, or findings on CXR, or physical examination (p trend >0.25 for all). Similarly, KCCQ‐TSS was not significantly associated with echocardiographic markers of left ventricular filling pressure, pulmonary pressure or with N‐terminal pro‐B‐type natriuretic peptide level. Conclusions: Among patients hospitalized for AHF, at baseline, KCCQ‐TSS was not associated with pulmonary congestion assessed by LUS, CXR, or physical examination. These findings suggest that the profound reduction in KCCQ‐TSS in patients with AHF may not be solely explained by pulmonary congestion. [ABSTRACT FROM AUTHOR]

Aims: Cardiac decompensation in aortic stenosis (AS) involves extra-valvular cardiac damage and progressive fluid overload (FO). FO can be objectively quantified using bioimpedance spectroscopy. We aimed to assess the prognostic value of FO beyond established damage markers to guide risk stratification., Methods and Results: Consecutive patients with severe AS scheduled for transcatheter aortic valve implantation (TAVI) underwent prospective risk assessment with bioimpedance spectroscopy (BIS) and echocardiography. FO by BIS was defined as ≥1.0 L (0.0 L = euvolaemia). The extent of cardiac damage was assessed by echocardiography according to an established staging classification. Right-sided cardiac damage (rCD) was defined as pulmonary vasculature/tricuspid/right ventricular damage. Hospitalization for heart failure (HHF) and/or death served as primary endpoint. In total, 880 patients (81 ± 7 years, 47% female) undergoing TAVI were included and 360 (41%) had FO. Clinical examination in patients with FO was unremarkable for congestion signs in >50%. A quarter had FO but no rCD (FO+/rCD-). FO+/rCD+ had the highest damage markers, including N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels. After 2.4 ± 1.0 years of follow-up, 236 patients (27%) had reached the primary endpoint (29 HHF, 194 deaths, 13 both). Quantitatively, every 1.0 L increase in bioimpedance was associated with a 13% increase in event hazard (adjusted hazard ratio 1.13, 95% confidence interval 1.06-1.22, p < 0.001). FO provided incremental prognostic value to traditional risk markers (NT-proBNP, EuroSCORE II, damage on echocardiography). Stratification according to FO and rCD yielded worse outcomes for FO+/rCD+ and FO+/rCD-, but not FO-/rCD+, compared to FO-/rCD-., Conclusion: Quantitative FO in patients with severe AS improves risk prediction of worse post-interventional outcomes compared to traditional risk assessment., (© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

The left atrium is a dynamic chamber with peculiar characteristics. Stressors and disease mechanisms may deeply modify its structure and function, leading to left atrial remodelling and disease. Left atrial disease is a predictor of poor outcomes. It may be a consequence of left ventricular systolic and diastolic dysfunction and neurohormonal and inflammatory activation and/or actively contribute to the progression and clinical course of heart failure through multiple mechanisms such as left ventricular filling and development of atrial fibrillation and subsequent embolic events. There is growing evidence that therapy may improve left atrial function and reverse left atrial remodelling. Whether this translates into changes in patient's prognosis is still unknown. In this review we report current data about changes in left atrial size and function across different stages of development and progression of heart failure. At each stage, drug therapies, lifestyle interventions and procedures have been associated with improvement in left atrial structure and function, namely a reduction in left atrial volume and/or an improvement in left atrial strain function, a process that can be defined as left atrial reverse remodelling and, in some cases, this has been associated with improvement in clinical outcomes. Further evidence is still needed mainly with respect of the possible role of left atrial reverse remodelling as an independent mechanism affecting the patient's clinical course and as regards better standardization of clinically meaningful changes in left atrial measurements. Summarizing current evidence, this review may be the basis for further studies. [ABSTRACT FROM AUTHOR]

Aims: This study investigated left atrial (LA) parameters as measured on transthoracic echocardiography as predictors of incident heart failure (HF) in a community cohort. Methods and results: In a large general population study (n = 2221), participants underwent a health examination with echocardiography. The maximum and minimum LA volumes indexed to body surface area (LAVImax and LAVImin) were measured and the LA emptying fraction (LAEF) and LA expansion index (LAEI) were calculated. Among 1951 participants without atrial fibrillation or significant valve disease, the mean age was 59 ± 16 years and 58% were women. At baseline, 1% (n = 16) had a left ventricular ejection fraction of <50%, 44% had hypertension, and 10% had diabetes. During follow‐up (median 15.8 years, interquartile range: 11.3–16.2 years), 187 (10%) participants were diagnosed with incident HF. Participants who were diagnosed with HF during follow‐up had a larger LAVImax and LAVImin and a lower LAEF and LAEI compared to participants without HF. In unadjusted analysis, LAVImax, LAVImin, LAEF and LAEI were predictors of incident HF. After multivariable adjustment for clinical and echocardiographic parameters, only LAVImin remained an independent predictor of incident HF (hazard ratio per 1 standard deviation increase: 1.22 [95% confidence interval 1.01–1.47], p = 0.038). Conclusion: In the general population, LAVImin is an independent predictor of incident HF. LAVImax, currently the only LA measure in a routine echocardiographic examination, was not an independent predictor of incident HF. [ABSTRACT FROM AUTHOR]

Aims: Congestion is a cardinal feature of untreated heart failure (HF) and might be detected by ultrasound (US) before overt clinical signs appear. Methods and results: We investigated the prevalence and clinical associations of subclinical congestion in 238 patients with at least one clinical risk factor for HF (diabetes, ischaemic heart disease, or hypertension) using three US variables: (i) inferior vena cava (IVC) diameter; (ii) jugular vein distensibility (JVD) ratio (the ratio of the jugular vein diameter during the Valsalva manoeuvre to that at rest); (iii) the number of B‐lines from a 28‐point lung US. US congestion was defined as IVC diameter > 2.0 cm, JVD ratio < 4.0 or B‐lines count > 14. The prevalence of subclinical congestion (defined as at least one positive US marker of congestion) was 30% (13% by IVC diameter, 9% by JVD ratio and 13% by B‐line quantification). Compared to patients with no congestion on US, those with at least one marker had larger left atria and higher plasma concentrations of natriuretic peptides. Patients with raised plasma N‐terminal pro‐B‐type natriuretic peptide/B‐type natriuretic peptide had a lower JVD ratio (7.69 vs. 8.80; P = 0.05) and more often had at least one lung B‐line (74% vs. 63%; P = 0.05). However, plasma natriuretic peptide concentrations were more closely related to left atrial volume than other US measures of congestion. Conclusions: Subclinical evidence of congestion by US is common in patients with clinical risk factors for HF. Whether these measurements provide additional value for predicting the development of HF and its prevention deserves consideration. [ABSTRACT FROM AUTHOR]

Congestion, related to pressure and/or fluid overload, plays a central role in the pathophysiology, presentation and prognosis of heart failure and is an important therapeutic target. While symptoms and physical signs of fluid overload are required to make a clinical diagnosis of heart failure, they lack both sensitivity and specificity, which might lead to diagnostic delay and uncertainty. Over the last decades, new ultrasound methods for the detection of elevated intracardiac pressures and/or fluid overload have been developed that are more sensitive and specific, thereby enabling earlier and more accurate diagnosis and facilitating treatment strategies. Accordingly, we considered that a state‐of‐the‐art review of ultrasound methods for the detection and quantification of congestion was timely, including imaging of the heart, lungs (B‐lines), kidneys (intrarenal venous flow), and venous system (inferior vena cava and internal jugular vein diameter). [ABSTRACT FROM AUTHOR]

Aims: Chronic hyperglycaemia, assessed by elevated glycated haemoglobin (A1C), is a known risk factor for heart failure (HF) and cardiovascular (CV) death among subjects with diabetes. Whether this risk varies with left ventricular ejection fraction (LVEF) is unknown. This study evaluated whether A1C influences a composite outcome of either HF hospitalization or CV death differently along the spectrum of LVEF.Methods and Results: We assessed the relationships of baseline A1C and LVEF with a composite outcome of either CV death or HF hospitalization in the 4091 patients with type 2 diabetes and a recent acute coronary syndrome enrolled in the ELIXA trial who had available LVEF. We assessed for interaction between A1C and LVEF as continuous variables with respect to this outcome. During a median follow-up of 25.7 months, 343 patients (8.4%) had HF hospitalization or died of CV causes. In a multivariable model, A1C and LVEF were each associated with an increased risk of HF hospitalization or CV death [adjusted hazard ratio (HR) 1.11, 95% confidence interval (CI) 1.01-1.21 per 1% higher A1C, and adjusted HR 1.39, 95% CI 1.27-1.51 per 10% lower in LVEF]. Both A1C and LVEF were independently and incrementally associated with risk without evidence of interaction (P for interaction = 0.31). Patients with A1C ≥ 8% and LVEF <40% were at threefold higher risk than those with A1C < 7% and LVEF ≥50% (adjusted HR 3.18, 95% CI 2.03-4.98, P < 0.001).Conclusion: In a contemporary cohort of patients with type 2 diabetes and acute coronary syndrome, baseline chronic hyperglycaemia was associated with an increased risk of HF hospitalization or CV death independently of LVEF. [ABSTRACT FROM AUTHOR]

Aims: Impact of type 2 diabetes mellitus (T2DM) on non-thromboembolic outcomes in atrial fibrillation (AF) is insufficiently explored. This prospective cohort study of AF patients aimed (i) to analyse the association between T2DM and heart failure (HF) events (including new-onset HF), and all-cause and cardiovascular mortality, (ii) to assess the impact of baseline T2DM treatment on outcomes, and (iii) to explore characteristics of new-onset HF phenotypes in relation to T2DM status.Methods and Results: Of 1803 AF patients (515/1288, with/without prior HF), 389 (22%) had T2DM at baseline. After 5 years of median follow-up, T2DM patients had an 85% greater risk of HF events [adjusted hazard ratio (aHR) 1.85; 95% confidence interval (CI) 1.51-2.28; P < 0.001], including a 45% increased risk for new-onset HF (1.45; 1.17-2.28; P = 0.015). T2DM conferred a 56% higher all-cause (1.56, 1.22-2.01; P = 0.003) and a 48% higher cardiovascular mortality (1.48; 1.34-1.93; P = 0.007). Fine-Gray analysis, with mortality as a competing risk, confirmed greater HF risk among T2DM patients. All risks were highest among insulin-treated patients. The prevalence of new-onset HF phenotypes was as follows: 67% preserved ejection fraction (HFpEF), 20% mid-range ejection fraction (HFmrEF) and 13% reduced ejection fraction (HFrEF). On time-dependent Cox regression, adjusted for baseline characteristics and an interim acute coronary event, T2DM increased aHRs for new-onset HFpEF (2.38; 1.30-4.58; P <0.001) and the combined HFmrEF/HFrEF (1.77; 1.11-3.62; P = 0.017).Conclusions: Atrial fibrillation patients with T2DM have independently increased risk of new-onset/recurrent HF events, cardiovascular and all-cause mortality, particularly when insulin-treated. The prevailing phenotype of new-onset HF was HFpEF; T2DM conferred higher risk of both HFpEF and HFmrEF/HFrEF. [ABSTRACT FROM AUTHOR]

Aims: The present study aimed to assess the association between left atrial (LA) structure and function and the risk for cardiovascular (CV) death or heart failure (HF) hospitalization in a population with atrial fibrillation (AF).Methods and Results: In a prospective echocardiographic substudy of the Effective Anticoagulation with Factor Xa Next Generation in AF-Thrombolysis in Myocardial Infarction 48 (ENGAGE AF-TIMI 48) study, 971 patients underwent transthoracic echocardiography. The associations between LA structure (LA volume index [LAVi]) and function (LA emptying fraction [LAEF] and LA expansion index [LAEi]) and risk for the composite endpoint of CV death or HF hospitalization, and its components, were assessed. Over a median follow-up of 2.5 years, 142 patients (14.6%) experienced CV death or HF hospitalization. Higher LAVi and lower LAEF and LAEi were each associated with a higher unadjusted risk for the composite outcome and its components. After adjustment for clinical and echocardiographic confounders, only measures of impaired LA function were predictive of the composite outcome (hazard ratio [HR] per 1 standard deviation [SD] decrease in LAEF: 1.35; 95% confidence interval [CI] 1.09-1.67 [P = 0.005]; HR per 1 SD decrease in LAEi: 1.34; 95% CI 1.06-1.69 [P = 0.012]). These findings were similar regardless of left ventricular ejection fraction, history of HF or whether patients were in AF or sinus rhythm at the time of the echocardiographic examination.Conclusions: In patients with AF, LA dysfunction was significantly associated with an increased risk for CV death or HF hospitalization and was more predictive of these outcomes than LA size. These parameters may help to identify AF patients at greatest risk for the development of HF.Clinical Trial Registration: ClinicalTrials.gov, NCT00781391. [ABSTRACT FROM AUTHOR]

Aims: Lung ultrasound (LUS) is a useful tool with which to assess subclinical pulmonary congestion and to stratify the prognosis of patients with heart failure (HF). The aim of this study was to evaluate whether an LUS-guided follow-up protocol improves the outcomes of patients with HF.Methods and Results: In this single-blind clinical trial, 123 patients admitted for HF were randomized to either a standard follow-up (n = 62, control group) or a LUS-guided follow-up (n = 61, LUS group). The primary endpoint was a composite of urgent visit, hospitalization for worsening HF and death during follow-up. Visits were scheduled at 14, 30, 90 and 180 days after discharge. Treating physicians were encouraged to modify diuretic therapy in accordance with the number of B-lines recorded by LUS. The mean ± standard deviation (SD) age of the patients was 69 ± 12 years and 72% were male. The mean ± SD left ventricular ejection fraction was 39 ± 14%. The hazard ratio for the primary outcome in the LUS group was 0.518 [95% confidence interval (CI) 0.268-0.998; P = 0.049], mainly resulting from a decrease in the number of urgent visits for worsening HF. The number of patients needed to treat to avoid an event was 5 (95% CI 3-62). Other secondary endpoints such as N-terminal pro-B-type natriuretic peptide reduction were not achieved. The safety parameters were similar in the two groups. Patients in the LUS group received more loop diuretics [51 (91%) vs. 42 (75%); P = 0.02] and showed an improvement in the distance achieved in the 6-min walking test [60 m (interquartile range: 29-125 m) vs. 37 m (interquartile range: 5-70 m); P = 0.023].Conclusions: Tailored LUS-guided diuretic treatment of pulmonary congestion in this proof-of-concept study reduced the number of decompensations and improved walking capacity in patients with HF. LUS is a non-invasive, safe and easy-to-use technique with potential clinical applicability to guide pulmonary congestion treatment in patients with HF. [ABSTRACT FROM AUTHOR]

Aims: An implantable cardioverter-defibrillator (ICD) is recommended for reducing the risk of sudden cardiac death (SCD) in myocardial infarction (MI) patients with a left ventricular ejection fraction (LVEF) ≤ 30%, as well as patients with a LVEF ≤ 35% and heart failure symptoms. Diabetes and/or impaired kidney function may confer additional SCD risk. We assessed the association between these two risk factors with SCD and non-SCD among MI survivors taking account of age and LVEF.Methods and Results: A total of 17 773 patients from the High-Risk MI Database were evaluated. Overall, diabetes and estimated glomerular filtration rate < 60 mL/min/1.73 m2 , individually and together, conferred a higher risk of SCD [adjusted competing risk: hazard ratio (HR) 1.23, 1.23, and 1.32, respectively; all P < 0.03] and non-SCD (HR 1.34, 1.52, and 2.13, respectively; all P < 0.0001). Annual SCD rates in patients with LVEF > 35% and with diabetes, impaired kidney function, or both (2.0%, 2.5% and 2.7%, respectively) were comparable to rates observed in patients with LVEF 30-35% but no such risk factors (1.7%). However, these patients had also similarly higher non-SCD rates, such that the ratio of SCD to non-SCD was not increased. Importantly, this ratio was mostly dependent on age, with higher overall ratios in youngest subgroups (0.89 in patients < 55 years vs. 0.38 in patients ≥ 75 years), regardless of risk factors.Conclusion: Although MI survivors with LVEF > 35% with diabetes, impaired kidney function, or both are at increased risk of SCD, the risk of non-SCD risk is even higher, suggesting an extension of the current indication for an ICD to them is unlikely to be worthwhile. MI survivors with low LVEF and aged < 55 years are likely to have the greatest potential benefit from ICD implantation. [ABSTRACT FROM AUTHOR]

Lung ultrasound is a useful tool for the assessment of patients with both acute and chronic heart failure, but the use of different image acquisition methods, inconsistent reporting of the technique employed and variable quantification of 'B-lines,' have all made it difficult to compare published reports. We therefore need to ensure that future studies utilizing lung ultrasound in the assessment of heart failure adopt a standardized approach to reporting the quantification of pulmonary congestion. Strategies to improve patient care by use of lung ultrasound in the assessment of heart failure have been difficult to develop. In the present document, key aspects of standardization are discussed, including equipment used, number of chest zones assessed, the method of quantifying B-lines, the presence and timing of additional investigations (e.g. natriuretic peptides and echocardiography) and the impact of therapy. This consensus report includes a checklist to provide standardization in the preparation, review and analysis of manuscripts. This will serve as a guide for investigators and clinicians and enhance the quality and transparency of lung ultrasound research. [ABSTRACT FROM AUTHOR]

Aims: Even if treatment controls symptoms, patients with heart failure may still be congested. We aimed at assessing the prevalence and clinical relevance of congestion in outpatients with chronic heart failure.Methods and Results: We recorded clinical and ultrasound [lung B-lines; inferior vena cava (IVC) diameter; internal jugular vein diameter before and after a Valsalva manoeuvre (JVD ratio)] features of congestion in heart failure patients during a routine check-up. Of 342 patients who attended, predominantly in New York Heart Association class I or II (n = 257; 75%), 242 (71%) had at least one feature of congestion, either clinical (n = 139; 41%) or by ultrasound (n = 199; 58%). Amongst patients (n = 203, 59%) clinically free of congestion, 31 (15%) had ≥ 14 B-lines, 57 (29%) had a dilated IVC (> 2.0 cm), 38 (20%) had an abnormal JVD ratio (< 4), 87 (43%) had at least one of these, and 27 (13%) had two or more. During a median follow-up of 234 (interquartile range 136-351) days, 60 patients (18%) died or were hospitalized for heart failure. In univariable analysis, each clinical and ultrasound measure of congestion was associated with increased risk but, in multivariable models, only higher N-terminal pro-B-type natriuretic peptide and IVC, and lower JVD ratio, were associated with the composite outcome.Conclusions: Many patients with chronic heart failure with few symptoms have objective evidence of congestion and this is associated with an adverse prognosis. Whether using these measures of congestion to guide management improves outcomes requires investigation. [ABSTRACT FROM AUTHOR]

Aims: Despite our prior report suggesting heart failure (HF) risk reduction from cardiac resynchronization therapy with defibrillator (CRT-D) in mild HF patients with higher left ventricular ejection fraction (LVEF > 30%), data on mortality benefit in this cohort are lacking. We aimed to assess long-term mortality benefit from CRT-D in mild HF patients by LVEF > 30%.Methods and Results: Among 1274 patients with mild HF and left bundle branch block enrolled in MADIT-CRT, we analysed long-term effects of CRT-D vs. implantable cardioverter defibrillator (ICD) therapy only, and reverse remodelling to CRT-D (left ventricular end-systolic volume percent change ≥ median at 1 year), on all-cause mortality and HF for the LVEF ≤ 30% and LVEF > 30 subgroups using Kaplan-Meier and Cox analyses. During long-term follow-up, CRT-D vs. ICD was associated with reduction in all-cause mortality in both patients with LVEF > 30% and LVEF ≤ 30% [hazard ratio (HR) 0.47, 95% confidence interval (CI) 0.25-0.85, P = 0.036 vs. HR 0.69, 95% CI 0.49-0.98, P = 0.013, interaction P = 0.261]. The efficacy of CRT-D vs. ICD only to reduce HF was similar in those with LVEF above and below 30% (HR 0.36, 95% CI 0.35-0.61, P < 0.001 vs. HR 0.46, 95% CI 0.35-0.61, P < 0.001; interaction P = 0.342). Patients with CRT-D-induced reverse remodelling had significant mortality reduction when compared to ICD, with either LVEF > 30% or LVEF ≤ 30% (HR 0.17 and 0.39), but no mortality benefit was seen in patients with less reverse remodelling. HF events, however, were reduced in both CRT-D-induced high and low reverse remodelling vs. ICD only, in both LVEF subgroups.Conclusions: In MADIT-CRT, left bundle branch block patients with higher LVEF (> 30%) derive long-term mortality benefit from CRT-D when exhibiting significant reverse remodelling.Clinical Trial Registration: ClinicalTrials.gov ID NCT00180271, NCT01294449, and NCT02060110. [ABSTRACT FROM AUTHOR]

Aims: We tested the hypothesis that a machine learning (ML) algorithm utilizing both complex echocardiographic data and clinical parameters could be used to phenogroup a heart failure (HF) cohort and identify patients with beneficial response to cardiac resynchronization therapy (CRT).Methods and Results: We studied 1106 HF patients from the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization Therapy (MADIT-CRT) (left ventricular ejection fraction ≤ 30%, QRS ≥ 130 ms, New York Heart Association class ≤ II) randomized to CRT with a defibrillator (CRT-D, n = 677) or an implantable cardioverter defibrillator (ICD, n = 429). An unsupervised ML algorithm (Multiple Kernel Learning and K-means clustering) was used to categorize subjects by similarities in clinical parameters, and left ventricular volume and deformation traces at baseline into mutually exclusive groups. The treatment effect of CRT-D on the primary outcome (all-cause death or HF event) and on volume response was compared among these groups. Our analysis identified four phenogroups, significantly different in the majority of baseline clinical characteristics, biomarker values, measures of left and right ventricular structure and function and the primary outcome occurrence. Two phenogroups included a higher proportion of known clinical characteristics predictive of CRT response, and were associated with a substantially better treatment effect of CRT-D on the primary outcome [hazard ratio (HR) 0.35; 95% confidence interval (CI) 0.19-0.64; P = 0.0005 and HR 0.36; 95% CI 0.19-0.68; P = 0.001] than observed in the other groups (interaction P = 0.02).Conclusions: Our results serve as a proof-of-concept that, by integrating clinical parameters and full heart cycle imaging data, unsupervised ML can provide a clinically meaningful classification of a phenotypically heterogeneous HF cohort and might aid in optimizing the rate of responders to specific therapies. [ABSTRACT FROM AUTHOR]

Myriad advances in all fields of cardiac imaging have stimulated and reflected new understanding of cardiac performance, myocardial damage and the mechanisms of heart failure. In this paper, the Heart Failure Association assesses the potential usefulness of innovative imaging modalities in enabling more precise diagnostic and prognostic evaluation, as well as in guiding treatment strategies. Many new methods have gradually penetrated clinical practice and are on their way to becoming a part of routine evaluation. This paper focuses on myocardial deformation and three-dimensional ultrasound imaging; stress tests for the evaluation of contractile and filling function; the progress of magnetic resonance techniques; molecular imaging and other sound innovations. The Heart Failure Association aims to highlight the ways in which paradigms have shifted in several areas of cardiac assessment. These include reassessing of the simplified concept of ejection fraction and implementation of the new parameters of cardiac performance applicable to all heart failure phenotypes; switching from two-dimensional to more accurate and reproducible three-dimensional ultrasound volumetric evaluation; greater tissue characterization via recently developed magnetic resonance modalities; moving from assessing cardiac function and congestion at rest to assessing it during stress; from invasive to novel non-invasive hybrid techniques depicting coronary anatomy and myocardial perfusion; as well as from morphometry to the imaging of pathophysiologic processes such as inflammation and apoptosis. This position paper examines the specific benefits of imaging innovations for practitioners dealing with heart failure aetiology, risk stratification and monitoring, and, in addition, for scientists involved in the development of future research. [ABSTRACT FROM AUTHOR]

Aims: Pulmonary congestion is an important finding in patients with heart failure (HF) that can be quantified by lung ultrasound (LUS). We conducted a systematic review to describe dynamic changes in LUS findings of pulmonary congestion (B-lines) in HF and to examine the prognostic utility of B-lines in HF.Methods and Results: We searched online databases for studies conducted in patients with chronic or acute HF that used LUS to assess dynamic changes or the prognostic value of pulmonary congestion. We included studies in adult populations, published in English, and conducted in ≥25 patients. Of 1327 identified studies, 13 (25-290 patients) met the inclusion criteria: six reported on dynamic changes in LUS findings (438 patients) and seven on the prognostic value of B-lines in HF (953 patients). In acute HF, B-line number changed within as few as 3 h of HF treatment. In acute HF, ≥15 B-lines on 28-zone LUS at discharge identified patients at a more than five-fold risk for HF readmission or death. Similarly, in ambulatory patients with chronic HF, ≥3 B-lines on five- or eight-zone LUS marked those at a nearly four-fold risk for 6-month HF hospitalization or death.Conclusions: Lung ultrasound findings change rapidly in response to HF therapy. This technique may represent a useful and non-invasive method to track dynamic changes in pulmonary congestion. Furthermore, residual congestion at the time of discharge in acute HF or in ambulatory patients with chronic HF may identify those at high risk for adverse events. [ABSTRACT FROM AUTHOR]

Aims Left ventricular mechanical dyssynchrony has been described in heart failure with preserved ejection fraction ( HFpEF), but its prognostic significance is not known. Methods and results Of 3445 patients with HFpEF enrolled in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist ( TOPCAT) trial, dyssynchrony analysis was performed on 424 patients (12%) by multiple speckle tracking echocardiography strain-based criteria. The primary dyssynchrony analysis was the standard deviation of the time to peak longitudinal strain ( SD T2P LS). Cox proportional hazards models assessed the association of dyssynchrony with the composite outcome of cardiovascular death or heart failure hospitalization. Mean age was 70 ± 10 years, LVEF was 60 ± 8%, and QRS duration was 101 ± 27 ms. Worse dyssynchrony, reflected in SD T2P LS, was associated with wider QRS, prior myocardial infarction, larger LV volume and mass, and worse systolic (lower LVEF and global longitudinal strain) and diastolic (lower e' and higher E/e') function. During a median follow-up of 2.6 (interquartile range 1.5-3.8) years, 107 patients experienced the composite outcome. Worse dyssynchrony was associated with the composite outcome in unadjusted analysis [hazard ratio ( HR) 1.04, 95% confidence interval ( CI) 1.01-1.07; P = 0.021, per 10 ms increase], but not after adjusting for clinical characteristics, or after further adjustment for LVEF, AF, NYHA class, stroke, heart rate, creatinine, haematocrit, and QRS duration ( HR 1.03, 95% CI 0.99-1.06; P = 0.16, per 10 ms increase). Conclusion Worse LV mechanical dyssynchrony, assessed by speckle tracking echocardiography, is not an independent predictor of adverse outcomes in HFpEF, suggesting that mechanical dyssynchrony is unlikely to be an important mechanism underlying this syndrome. These findings warrant validation in an independent study specifically designed to assess the prognostic utility of mechanical dyssynchrony in HFpEF. Trial registration: NCT00094302 [ABSTRACT FROM AUTHOR]

Aims: A longitudinal and comprehensive analysis of health-related quality of life (HRQOL) was performed during hospitalization for heart failure (HF) or soon after discharge.Methods and Results: A post-hoc analysis was performed of the ASCEND-HF trial. The EuroQOL five dimensions questionnaire (EQ-5D) was administered to study participants at baseline, 24 h, discharge/day 10, and day 30. EQ-5D includes functional dimensions mapped to corresponding utility scores (i.e. 0 = death and 1 = perfect health), and a visual analogue scale (VAS) ranging from 0 (i.e. 'worst imaginable health state') to 100 (i.e. 'best imaginable health state'). The association between baseline and discharge EQ-5D measurements and subsequent clinical outcomes including death and rehospitalization were assessed using multivariable logistic regression and Cox proportional hazards regression. A total of 6943 patients (97%) had complete EQ-5D data at baseline. Mapped utility and VAS scores (mean ± SD) increased over time, respectively, from 0.56 ± 0.23 and 45 ± 22 at baseline to 0.67 ± 0.26 and 58 ± 22 at 24 h and to 0.79 ± 0.20 and 68 ± 22 at discharge, and remained stable at day 30. Lower mapped utility scores at baseline [odds ratio (OR) per 0.1 decrease in utility score 1.03, 95% confidence interval (CI) 1.00-1.06] and discharge (OR 1.10, 95% CI 1.05-1.15) and VAS scores at baseline (OR per 10 point decrease 1.05, 95% CI 1.01-1.09) were significantly associated with increased risk of 30-day all-cause death or HF rehospitalization.Conclusions: Patients hospitalized for HF had severely impaired health status at baseline and, although this improved substantially during admission, health status remained abnormal at discharge. [ABSTRACT FROM AUTHOR]

Aims: Serum uric acid (SUA) levels are associated with poorer outcomes in healthy cohorts and patients with stable and unstable coronary heart disease. We investigated the relationship between SUA and clinical outcomes in subjects with acute myocardial infarction (MI) complicated by reduced left ventricular (LV) function, heart failure (HF), or both.Methods and Results: Univariable and multivariable Cox proportional hazards modelling was performed to study the association of baseline SUA and all-cause mortality, cardiovascular (CV) mortality, and HF hospitalization in an individual patient meta-analysis of four merged large randomized trials (CAPRICORN, EPHESUS, OPTIMAAL, and VALIANT). Three trials (excluding VALIANT) reported SUA, which was available in a total of 12 677 subjects. The ranges of SUA for quartiles I-IV were 45-280, 281-344, 345-420, and 420-1640 mmol/L, respectively. While almost 90% of patients in the lowest SUA quartile were alive after a mean follow-up of 23 ± 11 months, <70% were alive in the highest SUA quartile. Compared with the lowest SUA quartile as reference, hazard ratios (HRs) and 95% confidence intervals (CIs) of SUA quartiles III and IV showed an increase in all-cause mortality [HR 1.18, 95% CI 0.95-1.46, and HR 1.36, 95% CI 1.11-1.67) and CV mortality (HR 1.27, 95% 1.01-1.61, and HR 1.47, 95% CI 1.17-1.83). SUA quartiles III and IV also exhibited increased HF hospitalization (HR 1.22, 95% CI 1.09-1.36, and HR 1.28, 95% CI 1.14-1.43; P < 0.001 for all comparisons) in multivariable analyses. The addition of SUA was associated with a significant improvement in reclassification to predict CV mortality (net reclassification improvement 17.6%, 95% CI 14.9-20.5%, P < 0.001).Conclusions: Elevated SUA is associated with poor outcomes in patients after MI complicated by reduced LV function, HF, or both. The quantification of SUA, a low-cost routinely available biomarker, could improve risk stratification of patients with complicated MI. [ABSTRACT FROM AUTHOR]

Aims: Residual pulmonary congestion at discharge is associated with poor prognosis in heart failure (HF), but its quantification through physical examination is challenging. Ultrasound imaging of lung comets (B-lines) could improve congestion evaluation. The aim of this study was to assess the short-term prognostic value of B-lines after discharge from HF hospitalisation compared with other indices of haemodynamic congestion (BNP, E/e', and inferior vena cava diameter) or clinical status (NYHA class).Methods and Results: Sixty consecutive HF inpatients underwent clinical examination, echocardiography, and lung ultrasound at discharge, independently of, and in addition to routine management by the attending physicians. The median B-line count was 8.5 (5-34). Three-month event-free survival for the primary endpoint (all-cause death or HF hospitalisation) was 27 ± 10% in patients with ≥30 B-lines and 88 ± 5% in those with <30 B-lines (P < 0.0001). In a multivariable model, ≥30 B-lines significantly predicted the combined endpoint (hazard ratio 5.66, 95% confidence interval 1.74-18.39, P = 0.04), along with NYHA ≥III and inferior vena cava diameter, while other indirect measures of congestion (BNP and E/e' ≥15) were not retained in the model; furthermore ≥30 B-lines independently also predicted the secondary outcomes (HF hospitalisation and death). Importantly, B-line addition to NYHA class and BNP was associated with improved risk classification (integrated discrimination improvement 15%, P = 0.02; continuous net reclassification improvement 65%, P = 0.03).Conclusion: Residual pulmonary congestion at discharge, as assessed by a B-line count ≥30, is a strong predictor of outcome. Lung ultrasonography may represent a useful tool to identify and monitor congestion and optimize therapy during and/or after hospitalisation for HF, which should be further validated in multicentre studies. [ABSTRACT FROM AUTHOR]

Aims: The use of an erythropoesis-stimulating agent, darbepoetin alfa (DA), to treat anaemia in patients with diabetes mellitus and chronic kidney disease was associated with a heightened risk of stroke and neutral efficacy in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), despite epidemiological data suggesting the contrary. However, this association has not been evaluated in another randomized, placebo-controlled trial.Methods and Results: Reduction of Events by Darbepoetin Alfa in Heart Failure (RED-HF) was a randomized placebo-controlled trial of DA in 2278 patients with systolic heart failure and anaemia, enrolled from 2006 to 2012 and followed for a median of 28 months. Within RED-HF, 816 patients had diabetes mellitus and chronic kidney disease [estimated glomerular filtration rate (eGFR) 20-60 mL/min/1.73 m(2) ] and met inclusion criteria for TREAT. TREAT-like RED-HF patient data were analysed alone and combined at the patient level with the 4038 TREAT patients. In RED-HF, the annualized event rate of stroke was 2.3 in patients on DA and 1.1 in patients randomized to placebo (P = 0.051). Analysis of the combined group (n = 4854) confirmed a nearly two-fold increase in stroke risk [hazard ratio (HR) 1.94, 95% confidence interval (CI) 1.43-2.63] and an overall neutral effect on mortality (HR 1.00, 95% CI 0.89-1.12) of raising haemoglobin with DA.Conclusion: The placebo-controlled cohort of heart failure patients with anaemia, diabetes mellitus, and chronic kidney disease from RED-HF provides confirmation of the increased stroke risk associated with DA use identified in TREAT. [ABSTRACT FROM AUTHOR]

Aim The aim of this study was to test the hypothesis that diabetes modifies the risk of mortality in acute heart failure patients, especially in patients with impaired LVEF, and that impaired LVEF in turn modifies the risk of mortality in diabetic patients. Methods and results We studied 2121 patients with acute heart failure admitted at two centres in Singapore from 1 January 2008 to 31 December 2009. The date of the last follow-up was 31 December 2011, with a median follow-up time (interquartile range) of 914 (442-1190) days. Cox regression was used to estimate hazard ratios for all-cause mortality in patients with LVEF ≥50%, LVEF 30-49%, and LVEF <30% relative to diabetic status. Impaired LVEF (<50%) in the presence of diabetes substantially increased the risk of mortality compared with non-diabetics with LVEF <50%. The adjusted hazard ratio ( aHR) and 95% confidence interval ( CI) for diabetic patients with an LVEF of 30-49% (1.46, 95% 1.18-1.81) was not statistically different from the aHR in non-diabetic patients with severely impaired LVEF of <30% (1.38, 95% CI 1.09-1.75) ( P = 0.644). The deleterious effects of diabetes seemed to be confined to acute heart failure patients with impaired LVEF, as the mortality rate in patients with LVEF >50% was not increased. Other clinical predictors of mortality were ageing, prior myocardial infarction, systolic blood pressure >140 mmHg, creatinine ≥250 µmol/L, haemoglobin <9.0 g/ dL, and prior stroke/transient ischaemic attack. Conclusion The interaction of diabetes and impaired LVEF in acute heart failure patients significantly amplifies the deleterious effects of each as distinct disease entities. [ABSTRACT FROM AUTHOR]

Aims Sudden cardiac death ( SCD) accounts for ∼ 25% of all deaths in heart failure with preserved ejection fraction ( HFpEF). However, strategies to identify HFpEF patients at a higher risk of SCD have not been developed. Methods and results We studied 4128 patients with HFpEF enrolled in the Irbesartan in Patients with Heart Failure and Preserved Ejection Fraction (I- PRESERVE) trial. All SCDs were adjudicated by a clinical endpoint committee. Cumulative incidences of SCD were estimated counting other deaths as competing risks. Cox regression analysis was used to generate a risk model for SCD. During a mean follow-up of 4.1 years, 231 (5.6%) patients died suddenly and 650 (15.7%) died non-suddenly. A multivariable model in 3480 patients including age, gender, history of diabetes and myocardial infarction, LBBB on ECG, and the natural logarithm of NT-proBNP identified a subgroup of 837 (24%) patients with ≥10% cumulative incidence of SCD over 5 years, accounting for other deaths as competing risk (Harrell's C index 0.75). The 5-year cumulative incidences of SCD in the higher and lower risk groups were 11% and 4%, respectively. In the higher risk group, 32% of deaths were SCD compared with 26% in the entire I- PRESERVE cohort. Conclusions A multivariable prediction model identified patients with HFpEF who have a ≥10% risk of SCD over 5 years, similar to the risk of SCD in the Sudden Cardiac Death in Heart Failure ( SCD-Heft) trial. This model may be useful for selecting patients with HFpEF for SCD prevention trials. [ABSTRACT FROM AUTHOR]

Aims Device-based pacing-induced diaphragmatic stimulation (PIDS) may have therapeutic potential for chronic heart failure (HF) patients. We studied the effects of PIDS on cardiac function and functional outcomes. Methods and results In 24 chronic HF patients with CRT, an additional electrode was attached to the left diaphragm. Randomized into two groups, patients received the following PIDS modes for 3 weeks in a different sequence: (i) PIDS off (control group); (ii) PIDS 0 ms mode (PIDS simultaneously with ventricular CRT pulse); or (iii) PIDS optimized mode (PIDS with optimized delay to ventricular CRT pulse). For PIDS optimization, acoustic cardiography was used. Effects of each PIDS mode on dyspnoea, power during exercise testing, and LVEF were assessed. Dyspnoea improved with the PIDS 0 ms mode ( P = 0.057) and the PIDS optimized mode ( P = 0.034) as compared with the control group. Maximal power increased from median 100.5 W in the control group to 104.0 W in the PIDS 0 ms mode ( P = 0.092) and 109.5 W in the PIDS optimized mode ( P = 0.022). Median LVEF was 33.5% in the control group, 33.0% in the PIDS 0 ms mode, and 37.0% in the PIDS optimized mode ( P = 0.763 and P = 0.009 as compared with the control group, respectively). PIDS was asymptomatic in all patients. Conclusion PIDS improves dyspnoea, working capacity, and LVEF in chronic HF patients over a 3 week period in addition to CRT. This pilot study demonstrates proof of principle of an innovative technology which should be confirmed in a larger sample. Trial registration NCT00769678. [ABSTRACT FROM AUTHOR]

Aims The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula estimates glomerular filtration rate (GFR) better than the simplified Modification of Diet in Renal Disease (sMDRD) formula in numerous populations. It has not previously been validated in heart failure patients. Methods and results The GFR was measured in 120 patients with chronic systolic heart failure (CHF) using [125I]iothalamate clearance (GFRIOTH) and estimated using the sMDRD and CKD-EPI equations. Accuracy, bias, and prognostic performance were compared. Cockcroft-Gault, CKD-EPI serum cystatin C, and CKD-EPI creatinine-serum cystatin C equations were compared in secondary analyses. Mean age was 59 ± 12 years, 80% were male. Mean LVEF was 29 ± 10%. Mean GFRIOTH was 74 ± 27 mL/min/1.73 m2, and mean estimated GFR was 66 ± 23 mL/min/1.73 m2 (CKD-EPI) and 63 ± 21 mL/min/1.73m2 (sMDRD). CKD-EPI showed less bias than sMDRD (-8 ± 15 vs. -11 ± 16 mL/min/1.73 m2, P < 0.001). Both equations underestimate at higher and overestimate at lower GFRIOTH. Eleven patients (9%) were accurately reclassified into lower CKD classes with CKD-EPI. Cockcroft-Gault showed lower bias (-3 ± 16 mL/min/1.73 m2) but worse precision and accuracy. Cystatin C-based estimation showed the lowest bias (-3 ± 14 mL/min/1.73 m2) and the best precision and accuracy. Prognostic value did not differ between all GFR estimates Conclusion The CKD-EPI equation more accurately estimates measured GFR than the sMDRD equation in CHF patients, with less bias and greater accuracy and precision. The prognostic power of all GFR assessments was equivalent. Based on better performance and equal risk prediction, we believe the CKI-EPI equation should be the preferred creatinine-based GFR estimation method in heart failure patients, particularly those with preserved or moderately impaired renal function. [ABSTRACT FROM AUTHOR]

Aims To compare the predictive value of estimated renal function calculated by the Chronic Kidney Disease Epidemiology Collaboration (eGFRCKD-EPI), four-variable Modification of Diet in Renal Disease (eGFRMDRD-4), and Cockcroft–Gault [estimated creatinine clearance (eCcr)] equation in terms of all-cause mortality in heart failure. Renal function is an important prognostic factor in heart failure. Established methods of estimating renal function are known to under-/overestimate true function in certain settings. Methods and results A total of 800 systolic heart failure outpatients (mean age 57 ± 11.5 years, 82% male) were studied over a median follow-up of 121 (Q1–Q3: 110–130) months. The highest systematic difference was seen between eCcr and eGFRMDRD-4 [+12.33 points (mean), 95% limits of agreement –22.35 to 47.01; generalized kappa = 0.36]. eGFRMDRD-4 and eGFRCKD-EPI were the most similar [–4.16 points (mean), 95% limits of agreement –11.56 to 3.25; generalized kappa = 0.74]. Up to 35.4% of patients were reclassified into different estimated glomerular filtration rate (eGFR) categories when comparing eGFRCKD-EPI with eCcr and eGFRMDRD-4. eGFRCKD-EPI performed marginally better in terms of predicting all-cause mortality than eGFRMDRD-4, as univariate areas under the time-dependent receiver operating characteristic curves (AUC), marginal and partial proportions of explained variation (PEV), net reclassification improvement (NRI), and the integrated discrimination improvement (IDI) for 5 years of follow-up were significantly higher for eGFRCKD-EPI than for eGFRMDRD-4. Conclusion In this cohort of heart failure patients, eGFRCKD-EPI was marginally better in predicting all-cause mortality than eGFRMDRD-4. Estimated function differed widely between equations and is likely to have an effect on therapy choice. [ABSTRACT FROM PUBLISHER]

Aims Chronic kidney disease (CKD) is a risk factor for left ventricular hypertrophy (LVH) and heart failure. We evaluated the effect of CKD on left ventricular (LV) remodelling among patients with mild heart failure. Methods and results REVERSE was a randomized, controlled trial evaluating cardiac resynchronization therapy (CRT) in patients with New York Heart Association (NYHA) class I/II heart failure. CKD was defined as an estimated glomerular filtration rate (eGFR) <60 mL/min/1.73 m2. We compared changes in LV function and size over the course of 12 months by CKD status using linear mixed models adjusted for demographics, co-morbidities, medications, cardiomyopathy aetiology, and CRT status. Finally, we evaluated the effect of CKD on cardiac remodelling among patients randomized to CRT on or off. CKD was associated with worsening LV function and dilation compared with the non-CKD group {adjusted, 12-month β coefficients for the CKD group compared with the non-CKD referent group: LV ejection fraction (%) [–1.80, 95% confidence interval (CI) –3.36 to –0.24], LV end-systolic volume (mL) (14.16, 95% CI 3.96–24.36), LV end-diastolic volume (mL) (14.88, 95% CI 2.88–26.76), LV end-systolic diameter (cm) (0.36, 95% CI 0.12–0.48), LV end-diastolic diameter (cm) (0.24, 95% CI 0.012–0.36), mitral regurgitation (%) (3.12, 95% CI 0.48–5.76), and LV shape (0.036, 95% CI 0.012–0.060)}. In participants assigned to CRT, those without CKD had significantly greater improvements in LV structural parameters compared with the CKD group. Conclusions In comparison with participants with normal kidney function, CKD is an independent risk factor for ventricular dysfunction and dilation. CRT improves LV function and structure to a lesser extent in patients with CKD than in those with normal kidney function. [ABSTRACT FROM PUBLISHER]

Aims The effect on left ventricular (LV) systolic function and LV dyssynchrony by alternative right ventricular (RV) lead position in cardiac resynchronization therapy (CRT) is unclear. In the present study, RV apical (RV-A) was compared with RV high posterior septal (RV-HS) lead position in CRT. Methods and results In 85 consecutive CRT patients (mean age 66 ±11 years) the RV lead placement was randomized to RV-A (n = 43) or RV-HS (n = 42). The LV lead was targeted to the latest activated LV segment (concordant LV lead), identified by two-dimensional speckle tracking radial strain (ST-RS) echocardiography. Concordant LV leads were obtained in 72%, similar in RV-A and RV-HS (79% vs. 64%; P = 0.13). Six months after CRT, no difference was found in LV reverse remodelling (reduction of LV end-systolic volume ≥15%) according to RV-A and RV-HS leads [26 (65%) vs. 25 (64%); P = 0.93]. Superior LV reverse remodelling was observed in concordant LV leads compared with discordant LV leads [41 (73%) vs. 10 (43%); P = 0.01]. At 6-month follow-up, LV reverse dyssynchrony (reduction of anteroseptal to posterior delay ≥50%) using ST-RS imaging was similar in RV-A and RV-HS [25 (63%) vs. 24 (62%); P = 0.93]. More LV reverse dyssynchrony was found in concordant LV leads vs. discordant LV leads [39 (70%) vs. 10 (43%); P = 0.03]. A concordant LV lead was an independent predictor of LV reverse remodelling (odds ratio, 3.65; P = 0.01) and LV reverse dyssynchrony (odds ratio, 4.22; P = 0.02) 6 months after CRT. Conclusion RV-A and RV-HS in CRT demonstrated similar LV reverse remodelling and LV reverse dyssynchrony at 6-month follow-up. Concordant LV leads provided superior LV reverse remodelling and LV reverse dyssynchrony. [ABSTRACT FROM PUBLISHER]

Aims We assessed the relationship between diabetes and cardiac structure and function following myocardial infarction (MI) and whether diabetes influences the effect of direct renin inhibition on change in left ventricular (LV) size. Methods and results The ASPIRE trial enrolled 820 patients 2–8 weeks after MI with ejection fraction ≤45% and randomized them to the direct renin inhibitor aliskiren (n= 423) or placebo (n = 397) added to standard medical therapy. Echocardiography was performed at baseline and after 36 weeks in 672 patients with evaluable paired studies. Compared with non-diabetic patients, diabetic patients (n = 214) were at higher risk for a composite of cardiovascular (CV) death, heart failure hospitalization, recurrent MI, stroke, or aborted sudden death (14 vs. 7%; adjusted hazard ratio 1.63, 95% confidence interval 1.01–2.64, P= 0.045), despite similar left ventricular ejection fraction (37.9 ± 5.3 vs. 37.6 ± 5.2%, P= 0.48) and end-systolic volume (ESV) (84 ± 25 vs. 82 ± 28 mL, P= 0.46). Diabetic patients demonstrated greater concentric remodelling (relative wall thickness 0.38 ± 0.07 vs. 0.36 ± 0.07, P= 0.0002) and evidence of higher LV filling pressure (E/E′ 11.1 ± 5.3 vs. 9.1 ± 4.3, P= 0.0011). At 36 weeks, diabetic patients experienced similar per cent reduction in ESV overall (−4.9 ± 17.9 vs. −5.5 ± 16.9, P= 0.67) but tended to experience greater reduction in ESV than non-diabetic patients when treated with aliskiren (interaction P = 0.08). Conclusions Compared with non-diabetic patients, diabetic patients are at increased risk of CV events post-MI despite no greater LV enlargement or reduction in systolic function. Diabetic patients demonstrate greater concentric remodelling and evidence of higher LV filling pressure, suggesting diastolic dysfunction as a potential mechanism for the higher risk observed among these patients. [ABSTRACT FROM PUBLISHER]

Aims Diagnosis and risk stratification of patients with heart failure remain a challenge. The small non-coding RNAs known as microRNAs regulate gene expression and seem to play an important role in the pathogenesis of heart failure. In the current study, we aim to characterize the levels of microRNAs in the sera of chronic systolic heart failure patients vs. controls and assess the possible correlation between elevation in the levels of specific microRNAs and clinical prognostic parameters in heart failure patients. Methods and results The levels of 186 microRNAs were measured in the sera of 30 stable chronic systolic heart failure patients and 30 controls using quantitative reverse transcription–polymerase chain reaction (qRT–PCR). The differences in microRNA levels between the two groups were characterized, and a score, based on the levels of four specific microRNAs with the most significant increase in the heart failure group (miR-423-5p, miR-320a, miR-22, and miR-92b), was defined. The score was used to discriminate heart failure patients from controls with a sensitivity and specificity of 90%. Moreover, in the heart failure group, there was a significant association between the score and important clinical prognostic parameters such as elevated serum natriuretic peptide levels, a wide QRS, and dilatation of the left ventricle and left atrium (r = 0.63, P = 3e-4; P = 0.009; P = 0.03; and P = 0.01, respectively). Conclusions Elevated serum levels of specific microRNAs: miR-423-5p, miR-320a, miR-22, and miR-92b, identify systolic heart failure patients and correlate with important clinical prognostic parameters. [ABSTRACT FROM PUBLISHER]

Heart failure is still a large medical problem, and the European Journal of Heart Failure remains dedicated to further investigating its pathophysiology and diagnosis, as well as alleviating the symptoms and improving outcome for patients with this disorder.1 In 2010, a large number of important studies have been published, many with exciting results. In this overview, we discuss the results of many of these studies, which have been conducted in a broad range of areas, ranging from pre-clinical research, to co-morbidities, new insights in the genetics of heart failure, and novel guidelines in the field of device therapy. [ABSTRACT FROM PUBLISHER]

Aims Randomized clinical trials have suggested that treatment of anaemia with erythropoiesis-stimulating agents (ESAs) in patients with cancer or chronic kidney disease may increase cardiovascular risk. We therefore examined the effect of treating anaemia with an ESA in patients with heart failure in a meta-analysis of randomized clinical trials, including the recently reported TREAT study. Methods and results We performed a systematic review and meta-analysis of all prospective, randomized, controlled studies of ESAs enrolling patients with heart failure and reporting data on mortality or non-fatal heart failure events. Of 10 trials initially identified by our search strategy, we pooled data from 9 placebo-controlled studies enrolling a total of 2039 patients, of whom 1023 (50.2%) were allocated to ESA treatment. The pooled risk ratio for ESA treatment relative to placebo was 1.03 [95% confidence interval (CI): 0.89-1.21, P = 0.68] for overall mortality and 0.95 (95% CI: 0.82-1.10, P = 0.46) for worsening heart failure. Conclusions The use of ESAs to manage anaemia in patients with heart failure was associated with a neutral effect on both mortality and non-fatal heart failure events. Definitive assessment of the balance of risk and benefit in this population awaits the completion of a randomized clinical trial adequately powered to assess clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: Patients with heart failure (HF) and anaemia have greater functional impairment, worse symptoms, increased rates of hospital admission, and a higher risk of death, compared with non-anaemic HF patients. Whether correcting anaemia can improve outcomes is unknown. [ABSTRACT FROM PUBLISHER]