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Aim: To investigate the association between the left atrial volume index (LAVI) and the incidence of cardiovascular events in patients with acute coronary syndrome (ACS) who did not have atrial fibrillation (AF)., Methods: In this sub-analysis of the HIJ-PROPER study, 226 ACS patients who did not have a history of AF were enrolled. Participants were divided into two groups according to the LAVI cut-off level calculated by receiver operating characteristic (ROC) curve analysis to predict the primary endpoint, and cardiovascular events were compared between groups. The primary endpoint was the first occurrence of all-cause death, non-fatal myocardial infarction, non-fatal stroke, and hospitalization for heart failure., Results: ROC curve analysis for the occurrence of composite of cardiovascular events indicated a LAVI cut-off point of 34 mL/m 2 . Based on this, 131 patients (58.0%) were in the LAVI < 34 mL/m 2 group and 95 (42.0%) were in the LAVI ≥ 34 mL/m 2 group. Over a median follow-up period of 4.0 years [interquartile range: 3.2, 5.1], cardiovascular events were noted in 7 and 15 patients in the LAVI < 34 mL/m 2 and LAVI ≥ 34 mL/m 2 groups, corresponding to an incidence rate of 5.3% and 15.8%, respectively. Patients with a LAVI value ≥ 34 mL/m 2 had a significantly higher risk of cardiovascular events than those with a LAVI value < 34 mL/m 2 (hazard ratio: 2.93; 95% confidence interval: 1.19-7.22; P = .014). The tendency was similar after adjusting for several confounders (P = .025)., Conclusion: In ACS patients without AF, elevated LAVI was associated with increased cardiovascular events., Clinical Trial Registration: International standard randomized controlled trial (URL: https://www.umin.ac.jp; UMIN000002742)., (© 2022 Wiley Periodicals LLC.)

Aims: Heart failure (HF) has shared genetic architecture with its risk factors: atrial fibrillation (AF), body mass index (BMI), coronary heart disease (CHD), systolic blood pressure (SBP), and type 2 diabetes (T2D). We aim to assess the association and risk prediction performance of risk‐factor polygenic risk scores (PRSs) for incident HF and its subtypes in bi‐racial populations. Methods and results: Five PRSs were constructed for AF, BMI, CHD, SBP, and T2D in White participants of the Atherosclerosis Risk in Communities (ARIC) study. The associations between PRSs and incident HF and its subtypes were assessed using Cox models, and the risk prediction performance of PRSs was assessed using C statistics. Replication was performed in the ARIC study Black and Cardiovascular Health Study (CHS) White participants. In 8624 ARIC study Whites, 1922 (31% cumulative incidence) HF cases developed over 30 years of follow‐up. PRSs of AF, BMI, and CHD were associated with incident HF (P < 0.001), where PRSAF showed the strongest association [hazard ratio (HR): 1.47, 95% confidence interval (CI): 1.41–1.53]. Only the addition of PRSAF to the ARIC study HF risk equation improved C statistics for 10 year risk prediction from 0.812 to 0.829 (∆C: 0.017, 95% CI: 0.009–0.026). The PRSAF was associated with both incident HF with reduced ejection fraction (HR: 1.43, 95% CI: 1.27–1.60) and incident HF with preserved ejection fraction (HR: 1.46, 95% CI: 1.33–1.62). The associations between PRSAF and incident HF and its subtypes, as well as the improved risk prediction, were replicated in the ARIC study Blacks and the CHS Whites (P < 0.050). Protein analyses revealed that N‐terminal pro‐brain natriuretic peptide and other 98 proteins were associated with PRSAF. Conclusions: The PRSAF was associated with incident HF and its subtypes and had significant incremental value over an established HF risk prediction equation. [ABSTRACT FROM AUTHOR]

Objectives: Heart failure exacerbations are a common cause of hospitalizations with a high readmission rate. There are few validated predictors of readmission after treatment for acute decompensated heart failure (ADHF). Lung ultrasound (LUS) is sensitive and specific in the assessment of pulmonary congestion; however, it is not frequently utilized to assess for congestion before discharge. This study assessed the association between number of B‐lines, on LUS, at patient discharge and risk of 30‐day readmission in patients hospitalized for acute decompensated heart failure (ADHF). Methods: This was a single‐center prospective study of adults admitted to a quaternary care center with a diagnosis of ADHF. At the time of discharge, the patient received an 8‐zone LUS exam to evaluate for the presence of B‐lines. A zone was considered positive if ≥3 B‐lines was present. We assessed the risk of 30‐day readmission associated with the number of lung zones positive for B‐lines using a log‐binomial regression model. Results: Based on data from 200 patients, the risk of 30‐day readmission in patients with 2–3 positive lung zones was 1.25 times higher (95% CI: 1.08–1.45), and in patients with 4–8 positive lung zones was 1.50 times higher (95% CI: 1.23–1.82, compared with patients with 0–1 positive zones, after adjusting for discharge blood urea nitrogen, creatinine, and hemoglobin. Conclusion: Among patients admitted with ADHF, the presence of B‐lines at discharge was associated with a significantly increased risk of 30‐day readmission, with greater number of lung zones positive for B‐lines corresponding to higher risk. [ABSTRACT FROM AUTHOR]

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: Hypoxia‐inducible factor‐prolyl hydroxylase (HIF‐PH) inhibitors have been developed for the treatment of renal anaemia; however, no study has evaluated the safety and efficacy of HIF‐PH inhibitors in patients with heart failure (HF). This study was designed to evaluate the safety and efficacy of daprodustat, a HIF‐PH inhibitor, in patients with HF and renal anaemia. Methods and results: We designed a pilot, multi‐centre, open‐label, randomized controlled study, in which 50 patients with HF complicated with chronic kidney disease and anaemia will be randomized 1:1 to either the daprodustat or control group at seven sites in Japan. Study entry requires New York Heart Association Class II HF symptoms or a history of hospitalization due to HF, an estimated glomerular filtration rate of <60 mL/min/1.73 m2, and a haemoglobin level of 7.5 to <11.0 g/dl. Patients randomized to the daprodustat group will be treated with oral daprodustat, and the dose will be uptitrated according to the changes in the haemoglobin level from previous visits. In this study, we will evaluate the impact of HIF‐PH inhibitors on cardiac function using advanced cardiovascular imaging modalities, including cardiac magnetic resonance imaging. The primary outcome is the haemoglobin level at 16 weeks of randomization, and all adverse events will be recorded and evaluated for any association with daprodustat treatment. Conclusion: Considering the hypothetical upside and downside of using HIF‐PH inhibitors in anaemic patients with HF and chronic kidney disease, and because there are virtually no safe and effective treatments for patients with anaemia not caused by iron deficiency, our study results will contribute significantly to this field. [ABSTRACT FROM AUTHOR]

Aims: We aim to investigate the additive effect of B‐lines on lung ultrasound (LUS) for predicting outcome in patients with heart failure (HF) when combined with conventional assessment of clinical congestion. Methods and results: This study prospectively enrolled 117 hospitalized HF patients (61 ± 16 years, 70.1% males) who underwent congestion assessment by the 'wet/dry' status, clinical congestion score (CCS), and B‐lines on LUS. The primary endpoint was all‐cause mortality or hospitalization for HF during the 180‐day follow‐up after discharge. The 'Wet', CCS ≥ 3, and B‐lines >5, indicators of congestion positive (+), were observed in 83.8%, 76.1%, and 70.1% of the patients on admission, respectively; and the numbers significantly decreased to 41.9%, 41.9%, and 35.9% at discharge, respectively. The agreement between the 'wet/dry' status and B‐lines (58.1%) or between CCS and B‐lines (56.4%) was moderate at discharge, in terms of both positive and both negative. By incorporating the B‐lines with assessment of clinical congestion, the patients at discharge were divided into three phenotypes as clinical congestion (+), clinical congestion (−) with B‐lines (+), and clinical congestion (−) with B‐lines (−). The Kaplan–Meier analysis showed a better survival in the both (−) group ('wet/dry' with B‐lines: Chi‐square 10.591, P = 0.005; CCS with B‐lines: χ2 6.239, P = 0.031). When the 'wet' patients (n = 49) being taken as the reference, the 'dry' patients with B‐lines (+) (n = 21) had an identical risk of the composite endpoint (hazard ratio [HR] adjusted for clinical covariates 1.021, 95% confidence interval [CI] 0.480–2.134, P = 0.974), while the 'dry' patients with B‐lines (−) (n = 47) had a lower risk (HR 0.264, 95% CI 0.113–0.617, P = 0.002). When the CCS (+) patients (n = 49) being regarded as the reference, similar results were obtained in the patients with CCS (−) but B‐lines (+) (n = 22) (HR 1.348, 95% CI 0.627–2.896, P = 0.444) as well as in those with both CCS (−) and B‐lines (−) (n = 46) (HR 0.447, 95% CI 0.202–0.992, P = 0.048). Conclusions: The combination of B‐lines on LUS and conventional assessment helped to identify new phenotypes of congestion that aid in the risk stratification of discharged HF patients. Further investigation is warranted to determine whether this strategy could be adopted as a guide for decongestion therapy. [ABSTRACT FROM AUTHOR]

Background: Patients with acute myocardial infarction (MI) are at high risk of upcoming events, in particular heart failure (HF), but reliable stratification methods are lacking. Our goal was to evaluate the potential role of circulating miRNAs as prognostic biomarkers in patients presenting with MI. Methods and results: We conducted a prospective study among 311 consecutive patients hospitalized with MI (65% ST‐segment elevation MI & median age of 55 years) with long‐term follow‐up. An initial screening was conducted to select candidate miRNAs, with subsequent study of 14 candidate miRNAs. The primary outcome was the composite of hospital admission for HF or cardiovascular death. During a mean follow‐up of 2.1 years miR‐21‐5p, miR‐23a‐3p, miR27b‐3p, miR‐122‐5p, miR210‐3p, and miR‐221‐3p reliably predicted the primary outcome. Multivariate Cox regression analyses highlighted that miR‐210‐3p [hazard ratio (HR) 2.65 per 1 SD increase, P < 0.001], miR‐23a‐3p (HR 2.11 per 1 SD increase, P < 0.001), and miR‐221‐3p (HR 2.03 per 1 SD increase, P < 0.001) were able to accurately predict the primary outcome, as well as cardiovascular death, HF hospitalizations, and long‐term New York Heart Association (NYHA) functional class. These three miRNAs clearly improved the performance of multivariate clinical models: ΔC‐statistic = 0.10 [95% confidence interval (CI), 0.03–0.17], continuous net reclassification index = 34.8% (95%CI, 5.8–57.4%), and integrated discrimination improvement (P < 0.001). Conclusions: This is the largest study evaluating the prognostic value of circulating miRNAs for HF‐related events among patients with MI. We show that several miRNAs predict HF hospitalizations, cardiovascular mortality, and poor long‐term NYHA status and improve current risk prediction methods. [ABSTRACT FROM AUTHOR]

Aims: Pulmonary congestion (PC) expressed by residual lung ultrasound B‐lines (LUS‐BL) could exist in some discharged heart failure (HF) patients, which is a known determinant of poor outcomes. Detection efficacy for PC is suboptimal with widely used imaging modalities, like X‐ray or echocardiography, while lung ultrasound (LUS) can sufficiently detect PC by visualizing LUS‐BL. In this trial, we sought to evaluate the impact LUS‐BL‐guided intensive HF management post‐discharge on outcome of HF patients discharged with residual LUS‐BL up to 1 year after discharge. IMP‐OUTCOME is a prospective, single‐centre, single‐blinded, randomized cohort study, which is designed to investigate if LUS‐BL‐guided intensive HF management post‐discharge in patients with residual LUS‐BL could improve the clinical outcome up to 1 year after discharge or not. Methods and results: After receiving the standardized treatment of HF according to current guidelines, 318 patients with ≥3 LUS‐BL assessed by LUS within 48 h before discharge will be randomly divided into the conventional HF management group and the LUS‐BL‐guided intensive HF management group at 1:1 ratio. Patient‐related basic clinical data including sex, age, blood chemistry, imaging examination, and drug utilization will be obtained and analysed. LUS‐BL will be assessed at 2 month interval post‐discharge in both groups, but LUS‐BL results will be enveloped in the conventional HF management group, and diuretics will be adjusted based on symptom and physical examination results with or without knowing the LUS‐BL results. Echocardiography examination will be performed for all patients at 12 month post‐discharge. The primary endpoint is consisted of the composite of readmission for worsening HF and all‐cause death during follow up as indicated. The secondary endpoints consisted of the change in the New York Heart Association classification, Duke Activity Status Index, N terminal pro brain natriuretic peptide value, malignant arrhythmia event and 6 min walk distance at each designed follow up, echocardiography‐derived left ventricular ejection fraction, and number of LUS‐BL at 12 month post‐discharge. Safety profile will be recorded and managed accordingly for all patients. Conclusions: This trial will explore the impact of LUS‐BL‐guided intensive HF management on the outcome of discharged HF patients with residual LUS‐BL up to 1 year after discharge in the era of sodium‐glucose cotransporter‐2 inhibitors and angiotensin receptor blocker‐neprilysin inhibitor. Trial Registration: ClinicalTrials.gov: NCT05035459 [ABSTRACT FROM AUTHOR]

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]

Aim: Echo‐derived haemodynamic classification, based on forward‐flow and left ventricular (LV) filling pressure (LVFP) correlates, has been proposed to phenotype patients with heart failure and reduced ejection fraction (HFrEF). To assess the prognostic relevance of baseline echocardiographically defined haemodynamic profile in ambulatory HFrEF patients before starting sacubitril/valsartan. Methods and results: In our multicentre, open‐label study, HFrEF outpatients were classified into 4 groups according to the combination of forward flow (cardiac index; CI:< or ≥2.0 L/min/m2) and early transmitral Doppler velocity/early diastolic annular velocity ratio (E/e′: ≥ or <15): Profile‐A: normal‐flow, normal‐pressure; Profile‐B: low‐flow, normal‐pressure; Profile‐C: normal‐flow, high‐pressure; Profile‐D: low‐flow, high‐pressure. Patients were started on sacubitril/valsartan and followed‐up for 12.3 months (median). Rates of the composite of death/HF‐hospitalization were assessed by multivariable Cox proportional‐hazards models. Twelve sites enrolled 727 patients (64 ± 12 year old; LVEF: 29.8 ± 6.2%). Profile‐D had more comorbidities and worse renal and LV function. Target dose of sacubitril/valsartan (97/103 mg BID) was more likely reached in Profile‐A (34%) than other profiles (B: 32%, C: 24%, D: 28%, P < 0.001). Event‐rate (per 100 patients per year) progressively increased from Profile‐A to Profile‐D (12.0%, 16.4%, 22.9%, and 35.2%, respectively, P < 0.0001). By covariate‐adjusted Cox model, profiles with low forward‐flow (B and D) remained associated with poor outcome (P < 0.01). Adding this categorization to MAGGIC‐score and natriuretic peptides, provided significant continuous net reclassification improvement (0.329; P < 0.001). Intermediate and high‐dose sacubitril/valsartan reduced the event's risk independently of haemodynamic profile. Conclusions: Echocardiographically‐derived haemodynamic classification identifies ambulatory HFrEF patients with different risk profiles. In real‐world HFrEF outpatients, sacubitril/valsartan is effective in improving outcome across different haemodynamic profiles. [ABSTRACT FROM AUTHOR]

Aims: This study explored the association between socio‐economic status (SES) and mortality among patients hospitalized for heart failure (HF) in China. Methods and results: We used data from the China Patient‐centred Evaluative Assessment of Cardiac Events‐Prospective Heart Failure Study (China PEACE 5p‐HF Study), which enrolled patients hospitalized primarily for HF from 52 hospitals between 2016 and 2018. SES was measured using the income, employment status, educational attainment, and partner status. Individual socio‐economic risk factor (SERF) scores were assigned based on the number of coexisting SERFs, including low income, unemployed status, low education, and unpartnered status. We assessed the effects of SES on 1 year all‐cause mortality using Cox models. We used the Harrell c statistic to investigate whether SES added incremental prognostic information for mortality prediction. A total of 4725 patients were included in the analysis. The median (interquartile range) age was 67 (57–76) years; 37.6% were women. In risk‐adjusted analyses, patients with low/middle income [low income: hazard ratio (HR) 1.61, 95% confidence interval (CI) 1.21–2.14; middle income: HR 1.32, 95% CI 1.00–1.74], unemployment status (HR 1.43, 95% CI 1.10–1.86), low education (HR 1.25, 95% CI 1.03–1.53), and unpartnered status (HR 1.22, 95% CI 1.03–1.46) had a higher risk of death than patients with high income, who were employed, who had a high education level, and who had a partner, respectively. Compared with the patients without SERFs, those with 1, 2, 3, and 4 SERFs had 1.52‐, 2.01‐, 2.45‐, and 3.20‐fold increased risk of death, respectively. The addition of SES to fully adjusted model improved the mortality prediction, with increments in c statistic of 0.01 (P < 0.01). Conclusions: In a national Chinese cohort of patients hospitalized for HF, low income, unemployment status, low education, and unpartnered status were all associated with a higher risk of death 1 year following discharge. In addition, incorporating SES into a clinical‐based model could better identify patients at risk for death. Tailored clinical interventions are needed to mitigate the excess risk experienced by those socio‐economic deprived HF patients. [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]

Background: Heart failure (HF) complicating acute coronary syndrome (ACS) is a herald of adverse outcomes. In this systematic review, we investigated the prevalence of lung ultrasound (LUS) findings and their prognostic utility among patients with ACS. Methods: We searched the online databases PubMed, EMBASE, and Web of Science for studies (full‐text articles, published in English) that used LUS in adult patients with ACS [ST‐elevation myocardial infarction (STEMI), non‐ST‐elevation myocardial infarction (NSTEMI), and unstable angina]. Results: Of 462 studies screened, five prospective, observational investigations published between 2010 and 2021 including 1087 patients met our inclusion criteria. Two studies employed 28‐zone imaging protocols whereas three used eight‐zone protocols. The proportion of patients with a prior HF diagnosis was ≤ 5% in all studies. The prevalence of B‐lines was examined prior to or within 12 hours after coronary angiogram and reporting varied between studies due to different imaging protocols or quantification methods. A higher number of B‐lines on admission was associated with an increased risk for developing symptomatic HF during the baseline hospitalization and with a higher in‐hospital mortality rate using either 8 or 28‐zone protocols. A higher number of B‐lines at baseline was also associated with an increased risk of subsequent HF hospitalization or all‐cause death. Conclusions: Pulmonary congestion by LUS performed on admission appears to be a common finding among patients hospitalized for ACS and is associated with adverse in‐hospital and long‐term outcomes. Further investigations using standardized LUS protocols are warranted and have the potential to improve risk stratification in ACS. [ABSTRACT FROM AUTHOR]

Aims: In ambulatory patients with chronic heart failure (HF), congestion and decongestion assessment may be challenging. The aim of this study is to assess the value of lung ultrasound (LUS) in outpatients with HF in characterizing decompensation and recompensation, and in outcomes prediction. Methods and results: Heart failure outpatients attended to establish HF decompensation were included. LUS was blindly performed at baseline (LUS1) and at clinical recompensation (LUS2). B‐lines were counted in eight scanned areas. Diagnosis of no HF decompensation vs. right‐sided, left‐sided, or global HF decompensation, and patients' management were performed by physicians blinded to LUS1. Outcome was the composite of all‐cause death or HF‐related hospitalization. Two hundred and thirty‐three suspicions of HF decompensation were included in 187 patients (71.4 ± 11.3 years, 66.8% men). Mean B‐line (LUS1) was 17.6 ± 11.2 vs. 3.7 ± 4.5 for episodes with and without HF decompensation, respectively (P < 0.001). Global HF decompensation showed the highest number of B‐lines (20.6 ± 11), followed by left‐sided (19.7 ± 11.6) and right‐sided (13.5 ± 9.8). B‐lines declined to 6.9 ± 6.7 (LUS2) (P < 0.001 vs. LUS1) after treatment, within a mean time of 24.2 ± 23.7 days [median 13.5 days (interquartile range 6–40)]. B‐lines were significantly associated with the composite endpoint at 30 days (hazard ratio [HR] 1.04 [95% confidence interval 1.01–1.07], P = 0.02), but not at 60 (P = 0.22) or 180 days (P = 0.54). In multivariable analysis, B‐line number remained as an independent predictor of the composite endpoint at 30 days, [HR 1.04 (1.01–1.07), P = 0.014], with a 4% increase risk per B‐line added. B‐lines correlated significantly with CA125 (R = 0.30, P = 0.001). Conclusions: Lung ultrasound supports the diagnostic work‐up of congestion and decongestion in chronic HF outpatients and identifies patients at high risk of short‐term events. [ABSTRACT FROM AUTHOR]

Chronic heart failure is one of the common causes of hospitalization and death. Pulmonary congestion is the common disease feature of patients with chronic heart failure, which could be correctly diagnosed by lung ultrasound. Efficacy of lung ultrasound‐guided pulmonary congestion management for patients with acute heart failure is well documented, however, more evidence is needed to establish the clinical value of pulmonary congestion detection by lung ultrasound examination in patients with chronic heart failure. This review summarized current evidence related to the use and clinical value of pulmonary congestion assessment by lung ultrasound in patients with chronic heart failure, aiming to provide new suggestions on promoting the widespread use of lung ultrasound in patients with chronic heart failure to improve the quality of life and outcome of patients with chronic heart failure. [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]

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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: Heart failure (HF) and chronic obstructive pulmonary disease (COPD) are main causes of dyspnoea, and echocardiography and spirometry are essential investigations for these diagnoses. Our aim was to determine the prevalence of HF and COPD in a general population, also how the diseases may be identified, and to what extent their clinical characteristics differ. Methods and results: In the seventh survey of Tromsø study (2015–16), subjects aged 40 years or more were examined with echocardiography, spirometry, lung sound recordings, questionnaires, including the modified Medical Research Council (mMRC) questionnaire on dyspnoea, and N‐terminal pro‐brain natriuretic peptide analysis. A diagnosis of HF (HF with reduced ejection fraction, HF with mid‐range ejection fraction, or HF with preserved ejection fraction) or COPD was established according to current guidelines. Predictors of HF and COPD were evaluated by logistic regression and receiver operating characteristic curve analysis. A total of 7110 participants could be evaluated for COPD, 1624 for HF, and 1538 for both diseases. Age‐standardized prevalence of HF was 6.8% for women and 6.1% for men; the respective figures for COPD were 5.2% and 5.1%. Among the 1538 evaluated for both diseases, 139 subjects fulfilled the HF criteria, but only 17.1% reported to have the disease. Of those fulfilling the COPD criteria, 31.6% reported to have the disease. Shortness of breath at exertion was a frequent finding in HF; 59% of those with mMRC ≥2 had HF, while such shortness of breath was found in 24% among those with COPD. Reporting mMRC ≥2 had an odds ratio for HF of 19.5 (95% confidence interval 11.3–33.7), whereas the odds ratio for COPD was 6.3 (95% confidence interval 3.5–11.6). Current smoking was the strongest predictor of COPD but did not predict HF. Basal inspiratory crackles were significant predictors of HF in multivariable analysis. Among the subtypes of HF, an age <70 years was most frequently found in HF with reduced ejection fraction, in 51.7%. Clinical scores based on the predictive value in multivariable analysis of history, symptoms, and signs predicted HF and COPD with areas under the curve of 0.833 and 0.829, respectively. Conclusions: Study participants with HF and COPD were in most cases not aware of their condition. In general practice, when an elderly patient present with shortness of breath, both diseases should be considered. Previous cardiovascular disease points at HF, while a history of smoking points at COPD. The threshold should be low for ordering echocardiography or spirometry for verifying the suspected cause of dyspnoea. [ABSTRACT FROM AUTHOR]

Aims: Residual pulmonary congestion at hospital discharge can worsen the outcomes in patients with heart failure (HF) and can be detected by lung ultrasound (LUS). The aim of this study was to analyse the prevalence of subclinical pulmonary congestion at discharge and its impact on prognosis in patients admitted for acute HF. Methods and results: This is a post‐hoc analysis of the LUS‐HF trial. LUS was performed by the investigators in eight chest zones with a pocket device. Physical exam was subsequently performed by the treating physicians. Primary outcome was a combined endpoint of rehospitalization, unexpected visit for HF worsening or death at 6‐ month follow‐up. Subclinical pulmonary congestion at discharge was defined as the presence of ≥5 B‐lines in LUS in absence of rales in the auscultation employing the area under the ROC curve. At discharge, 100 patients (81%) did not show clinical signs of pulmonary congestion. Of these, 41 had ≥5 B‐lines. Independent factors related with the presence of subclinical pulmonary congestion were anaemia, higher New York Heart Association (NYHA) class, and N terminal pro brain natriuretic peptide (NT‐proBNP). After adjusting by propensity score analysis including age, renal insufficiency, atrial fibrillation, NYHA class, NT‐proBNP levels, clinical congestion, and the trial intervention, the presence of subclinical pulmonary congestion at discharge was a risk factor for the occurrence of the primary outcome (hazard ratio 2.63; 95% confidence interval: 1.08–6.41; P = 0.033). Conclusions: Up to 40% of patients considered 'dry' according to pulmonary auscultation presents subclinical congestion at hospital discharge that can be detected by LUS and implies a worse prognosis at 6‐ month follow‐up. Comorbidities, high values of natriuretic peptides, and higher NYHA class are the factors related with its presence. [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: Increased body mass index (BMI) is common in heart failure (HF) patients and is associated with lower levels of N‐terminal pro‐brain natriuretic peptide (NT‐proBNP). We evaluated the influence of BMI on lung ultrasonography (LUS) findings indicative of pulmonary congestion (i.e. B‐lines) in patients with chronic and acute HF (AHF). Methods and results: We analysed ambulatory chronic HF (n = 118) and hospitalized AHF (n = 177) patients (mean age 70 years, 64% men, mean BMI 29 kg/m2, mean ejection fraction 42%) undergoing echocardiography and LUS in eight chest zones. B‐lines and chest wall thickness (skin to pleura) on ultrasound were quantified offline and blinded to clinical findings. NT‐proBNP was available in AHF patients (n = 167). In chronic HF, B‐line number decreased by 18% per 5 unit increase in BMI [95% confidence interval (CI) −35% to +5%, P = 0.11]. In AHF, the number of B‐lines decreased by 12% per 5 unit increase in BMI (95% CI −19% to −5%, P = 0.001), whereas NT‐proBNP concentration decreased by 28% per 5 unit increase in BMI (95% CI −40% to −16%, P < 0.001). For AHF, B‐line number declined to a lesser degree than NT‐proBNP concentration with increasing BMI (P = 0.020), and >6 B‐lines were observed in half of AHF patients with severe obesity. There was an inverse relationship between B‐line number and chest wall thickness, and this association varied by chest region. Conclusions: Despite an inverse relationship between B‐lines and BMI, B‐lines declined to a lesser degree than NT‐proBNP with increasing BMI. These data suggest that LUS may be useful in patients with HF despite obesity. [ABSTRACT FROM AUTHOR]

Aims: Treating patients with acute decompensated heart failure (ADHF) presenting with volume overload is a common task. However, optimal guidance of decongesting therapy and treatment targets are not well defined. The inferior vena cava (IVC) diameter and its collapsibility can be used to estimate right atrial pressure, which is a measure of right‐sided haemodynamic congestion. The CAVA‐ADHF‐DZHK10 trial is designed to test the hypothesis that ultrasound assessment of the IVC in addition to clinical assessment improves decongestion as compared with clinical assessment alone. Methods and results: CAVA‐ADHF‐DZHK10 is a randomized, controlled, patient‐blinded, multicentre, parallel‐group trial randomly assigning 388 patients with ADHF to either decongesting therapy guided by ultrasound assessment of the IVC in addition to clinical assessment or clinical assessment alone. IVC ultrasound will be performed daily between baseline and hospital discharge in all patients. However, ultrasound results will only be reported to treating physicians in the intervention group. Treatment target is relief of congestion‐related signs and symptoms in both groups with the additional goal to reduce the IVC diameter ≤21 mm and increase IVC collapsibility >50% in the intervention group. The primary endpoint is change in N‐terminal pro‐brain natriuretic peptide from baseline to hospital discharge. Secondary endpoints evaluate feasibility, efficacy of decongestion on other scales, and the impact of the intervention on clinical endpoints. Conclusions: CAVA‐ADHF‐DZHK10 will investigate whether IVC ultrasound supplementing clinical assessment improves decongestion in patients admitted for ADHF. [ABSTRACT FROM AUTHOR]

Background: Vest Prevention of Early Sudden Death Trial did not demonstrate a significant reduction in arrhythmic death with the wearable cardioverter‐defibrillator (WCD), but compliance with the device may have substantially affected the results. ThePletcher influence of WCD compliance on outcomes has not yet been fully evaluated. Methods: Using linear and pooled logistic models, we performed as‐treated analyses omitting person‐time in the hospital and adjusted for correlates of WCD compliance. To assess the impact of early stopping of WCD, we performed a per‐protocol Kaplan‐Meier analysis, censoring after the last day the WCD was worn. Interactions of potential effect modifiers with treatment assignment and WCD compliance on outcomes were investigated. Finally, we used linear models to identify predictors of WCD compliance. Results: A per‐protocol analysis demonstrated a significant reduction in total (P <.001) and arrhythmic (P =.001) mortality. Better WCD compliance was independently predicted by cardiac arrest during index myocardial infarction (MI), higher Cr, diabetes, prior heart failure, EF ≤ 25%, Polish enrolling center and number of WCD alarms, while worse compliance was predicted by being divorced, Asian race, higher body mass index, prior percutaneous coronary intervention, or any WCD shock. Neither excluding time in hospital from the as‐treated analysis nor adjustment for factors affecting WCD compliance materially changed the results. No variable demonstrated a significant interaction in either the intention‐to‐treat or as‐treated analysis. Conclusion: Robust sensitivity analyses of as‐treated and per‐protocol analyses suggest that the WCD is protective in compliant patients with ejection fraction less than or equal to 35% during the first 3 months post‐MI. [ABSTRACT FROM AUTHOR]

Currently, the assessment of left ventricular ejection fraction (LVEF) is the cornerstone of the classification of patients with heart failure (HF). The mid‐range LVEF (HFmrEF) category was identified in an attempt to uncover specific characteristics of these patients. So far, the analysis of trials, registries, and observational studies have demonstrated that patients with mid‐range LVEF belong to a patient cohort with generally intermediate clinical profile as compared with other groups but with a remarkable variety of intrinsic phenotypes. This is due to the limitations of LVEF as the sole criterion to categorize patients with HF and characterize their prognosis, above all when it is >40%. To better define the HFmrEF phenotype, it is reasonable to consider other parameters, such as LVEF changes over time, HF aetiology, co‐morbidities, and other imaging parameters. A multiparametric evaluation may contextualize a patient with HFmrEF in a more defined phenotype with a specific prognosis. [ABSTRACT FROM AUTHOR]

Aims: The Treatment of Sleep‐Disordered Breathing with Predominant Central Sleep Apnoea by Adaptive Servo Ventilation in Patients with Heart Failure trial investigated the effects of adaptive servo‐ventilation (ASV) (vs. control) on outcomes of 1325 patients with heart failure and reduced ejection fraction (HFrEF) and central sleep apnoea (CSA). The primary outcome (a composite of all‐cause death or unplanned HF hospitalization) did not differ between the two groups. However, all‐cause and cardiovascular (CV) mortality were higher in the ASV group. Circulating biomarkers may help in better ascertain patients' risk, and this is the first study applying a large set of circulating biomarkers in patients with both HFrEF and CSA. Methods and results: Circulating protein‐biomarkers (n = 276) ontologically involved in CV pathways, were studied in 749 (57% of the trial population) patients (biomarker substudy), to investigate their association with the study outcomes (primary outcome, CV death and all‐cause death). The mean age was 69 ± 10 years, and > 90% were male. The groups (ASV vs. control and biomarker substudy vs. no biomarker) were well balanced. The "best" clinical prognostic model included male sex, systolic blood pressure < 120 mmHg, diabetes, loop diuretic, cardiac device, 6‐min walking test distance, and N‐terminal pro BNP as the strongest prognosticators. On top of the "best" clinical prognostic model, the biomarkers that significantly improved both the discrimination (c‐index) and the net reclassification index (NRI) of the model were soluble suppression of tumorigenicity 2 for the primary outcome; neurogenic locus notch homolog protein 3 (Notch‐3) for CV‐death and all‐cause death; and growth differentiation factor 15 (GDF‐15) for all‐cause death only. Conclusions: We studied 276 circulating biomarkers in patients with HFrEF and central sleep apnoea; of these biomarkers, three added significant prognostic information on top of the best clinical model: soluble suppression of tumorigenicity 2 (primary outcome), Notch‐3 (CV and all‐cause death), and GDF‐15 (all‐cause death). [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]

Objective: B‐line imaging by lung ultrasound (LUS) is a new tool for evaluating subclinical pulmonary congestion. The aim of this study was to explore the prognostic value of B‐line number at admission in predicting symptomatic heart failure (HF) during hospitalization in acute anterior wall STEMI patients. Methods: This was a prospective cohort study which consecutively enrolled 96 anterior wall STEMI patients without dyspnea at admission. Pulmonary auscultation, NT‐proBNP test, LUS, and echocardiography were performed within 5 hours after primary PCI. Rale occurrence, plasma NT‐proBNP levels, B‐line number, LVEF, E/e' were recorded, and their predictive value for HF in‐hospital was analyzed. Results: A total of 19 patients developed symptomatic HF. Median B‐line number, NT‐proBNP levels, and E/e' in the HF group were higher than those of the nonheart‐failure (NHF) group (P < 0.001) while LVEF was lower (P = 0.002). There was no statistical difference in rale occurrence between the two groups. Multivariate logistic regression demonstrated that B‐lines, E/e', and NT‐proBNP independently predicted HF during hospitalization. According to the area under the ROC curve, the strongest predictor is B‐lines (0.972), followed by NT‐proBNP (0.936) and E/e' (0.928), and combining the three indicators was better than any single parameter (P = 0.048). B‐line cutoff ≥18 could well predict HF event with specificity and sensitivity of 94.7% and 94.8%, respectively. Conclusion: Subclinical pulmonary congestion reflected by B‐lines can independently predict symptomatic HF during hospitalization in patients with anterior wall STEMI, LUS will act as a complementary tool for evaluating cardiac function. [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: 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]

Background: Prior studies have shown that both heart failure (HF) and atrial fibrillation (AF) are factors that impact left atrial function and structure. However, right atrial (RA) function measured as RA emptying fraction (RAEF) on echocardiography has not been analyzed systematically in a chronic HF population. The aim of this study was to assess RA volume index (RAVI) and RAEF in patients with chronic HF and patients with hypertension (HTN) and to relate these findings to other cardiopulmonary ultrasound parameters and 12‐month outcomes. Methods and Results: In this prospective observational study, we identified 119 patients with chronic HF (64 patients without a history of AF [HF without AF], 55 with AF [HF with AF]), and 127 patients with HTN but without important cardiac disease who underwent routine outpatient transthoracic echocardiography. We found that RAEF was impaired in patients with HF without AF compared to patients with HTN (35% ±2 vs 50% ±1, P < .001), whereas RAVI did not differ between these two groups. Lower RAEF was associated with larger RAVI and higher estimated RA pressures but not with a higher degree of pulmonary congestion by lung ultrasound. Both lower RAEF and higher RAVI were associated with an increased risk of 12‐month HF hospitalizations or all‐cause death (age, sex, and AF adjusted HR: 4.07, 95% CI: 1.69–9.79; P = .002, vs 2.74, 95% CI: 1.15–6.54, P = .023). Conclusions: In an outpatient HF cohort, both lower RAEF and increased RAVI were associated with other markers of impaired cardiac function and 12‐month adverse events. [ABSTRACT FROM AUTHOR]

Background: Left ventricular ejection fraction (LVEF) is fundamental for risk stratification after ST‐segment elevation myocardial infarction (STEMI). However, it lacks discrimination power within normal range. Novel echocardiographic deformation parameters may be of benefit for those with post‐MI preserved LVEF. Objectives: We hypothesized that semiautomated calculation of baseline global longitudinal strain (GLS) can identify high‐risk group among patients with LVEF ≥ 50% following STEMI. Methods: During the period from January to July 2017, 110 patients with successful reperfusion of STEMI and LVEF ≥ 50% were prospectively included. Within 48 hours, patients underwent a baseline GLS study with follow‐up study at 30 days. The endpoint was a composite of cardiovascular mortality, rehospitalization for heart failure, and urgent revascularization. Results: Mean GLS value changed from −16 ± 4% at baseline to −12 ± 4% at 30‐day follow‐up (P < .001). At 30 days, cardiovascular mortality was reported in 4.5%, 11.8% were rehospitalized due to heart failure, and 5.4% underwent urgent revascularization. ROC curve analysis showed that a cutoff baseline GLS value >−12.65% predicted 30‐day MACEs with a sensitivity and specificity of 77.8% and 83.7%, respectively (AUC 0.784, 95% CI 0.646–0.921, P < .001). An adjusted multivariate logistic regression analysis revealed that baseline GLS value >−12.65% to be the only significant independent predictor for occurrence of MACEs (OR 19.54, 95% CI 6.3–61.1, P < .001). Conclusion: Early GLS calculation predicts 30‐day outcome in patients with preserved LVEF following reperfusion of STEMI. [ABSTRACT FROM AUTHOR]

New Findings What is the central question of this study? Type 2 diabetes is associated with a higher rate of ventricular arrhythmias compared with the non-diabetic population, but the associated myocardial gene expression changes are unknown; furthermore, it is also unknown whether any changes are attributable to chronic hyperglycaemia or are a consequence of structural changes., What is the main finding and its importance? We found downregulation of left ventricular ERG gene expression and increased NCX1 gene expression in humans with type 2 diabetes compared with control patients with comparable left ventricular hypertrophy and possible myocardial fibrosis. This was associated with QT interval prolongation. Diabetes and associated chronic hyperglycaemia may therefore promote ventricular arrhythmogenesis independently of structural changes., Type 2 diabetes is associated with a higher rate of ventricular arrhythmias, and this is hypothesized to be independent of coronary artery disease or hypertension. To investigate further, we compared changes in left ventricular myocardial gene expression in type 2 diabetes patients with patients in a control group with left ventricular hypertrophy. Nine control patients and seven patients with type 2 diabetes with aortic stenosis undergoing aortic valve replacement had standard ECGs, signal-averaged ECGs and echocardiograms before surgery. During surgery, a left ventricular biopsy was taken, and mRNA expressions for genes relevant to the cardiac action potential were estimated by RT-PCR. Mathematical modelling of the action potential and calcium transient was undertaken using the O'Hara-Rudy model using scaled changes in gene expression. Echocardiography revealed similar values for left ventricular size, filling pressures and ejection fraction between groups. No difference was seen in positive signal-averaged ECGs between groups, but the standard ECG demonstrated a prolonged QT interval in the diabetes group. Gene expression of KCNH2 and KCNJ3 were lower in the diabetes group, whereas KCNJ2, KCNJ5 and SLC8A1 expression were higher. Modelling suggested that these changes would lead to prolongation of the action potential duration with generation of early after-depolarizations secondary to a reduction in density of the rapid delayed rectifier K+ current and increased Na+-Ca2+ exchange current. These data suggest that diabetes leads to pro-arrythmogenic changes in myocardial gene expression independently of left ventricular hypertrophy or fibrosis in an elderly population. [ABSTRACT FROM AUTHOR]

In heart failure patients, we hypothesize the occurrence of the 'lung water cascade,' with the various markers hierarchically ranked in a well-defined time sequence: (1) early, proximal hemodynamic event with increase in pulmonary capillary wedge pressure; (2) intermediate, direct imaging sign of pulmonary edema (easily detectable at bedside by lung ultrasound as B-lines); (3) late, distal clinical symptoms and signs such as dyspnea and pulmonary crackles. Completion of the cascade (from hemodynamic to pulmonary to clinical congestion) can require minutes (as with exercise), hours or even weeks (as with impending acute heart failure). Backward rewind of the downhill cascade can be achieved with timely pulmonary decongestion therapy, such as diuretics or dialysis, restoring a relatively dry lung. Any therapeutic intervention is more likely to succeed in the early steps of the cascade, at the imaging stage of asymptomatic pulmonary congestion, rather than downstream near to the end of the cascade, when clinical instability occurred. [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]

Objective: Preliminary data suggest that nonalcoholic fatty liver disease is associated with early heart failure (HF). However, whether nonalcoholic steatohepatitis (NASH) is directly associated with echocardiographic changes in cardiac structure or function remains unknown.Methods: A retrospective cohort was identified of individuals (N = 65) without known heart disease, undergoing elective bariatric surgery with perioperative liver biopsy, and available recent transthoracic echocardiography (TTE). TTE measures were evaluated by NASH status using correlation coefficients, ANOVA, and linear regression, accounting for cardiometabolic factors.Results: Median age was 47 years; 22% (n = 14) had NASH. NASH patients had increased median left atrial (LA) volume (28.6 mL/m2 vs. 24.8 mL/m2 ; P < 0.0001) and left ventricular (LV) mass (82.6 g/m2 vs. 78.6 g/m2 ; P < 0.0001), indexed for height. NASH was inversely correlated with indices of diastolic function, including septal E' (r = -0.90 [95% CI: -1.21 to -0.42]; P = 0.020) and E:A (r = -0.31 [95% CI: -0.51 to -0.09]; P = 0.037). In adjusted analyses, NASH remained associated with increased LV mass index (ß1  = 7.16 [SE: 4.95]; P = 0.001) and LA volume index (ß1  = 0.19 [SE: 0.08]; P = 0.001) and reduced lateral and septal E' (ß1  = -0.91, P = 0.015; ß1  = -0.89, P = 0.047, respectively).Conclusions: In this bariatric cohort, NASH was associated with changes in myocardial structure and in load-dependent indices of LV diastolic function, suggestive of subclinical HF. [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]

Background In dogs with chronic valvular heart disease (CVHD), early recognition of pulmonary edema (PE) is of paramount importance. Recent studies in dogs showed that lung ultrasound examination (LUS) is a useful technique to diagnose cardiogenic PE. Objectives To describe LUS features in dogs with different stages of CVHD, and to determine its diagnostic accuracy in detecting PE using thoracic radiography as the reference standard. Animals Sixty-three dogs with CVHD. Methods Prospective, multicenter, cross-sectional study. Each dog underwent physical examination, echocardiography, thoracic radiography, and LUS. The LUS findings were classified as absent, rare, numerous, or confluent B-lines. Sensitivity, specificity, and positive and negative predictive values of LUS B-lines to identify PE were calculated using thoracic radiography as the reference standard. Results Dogs in stage B1 had absent or rare B-lines in 14 of 15 cases (93.3%). Dogs in stage B2 had absent or rare B-lines in 16 of 18 cases (88.9%). All dogs in stage C, without radiographic signs of PE, had absent or rare B-lines. Dogs in stage C, with radiographic signs of PE, had numerous or confluent B-lines in 18 of 20 cases (90%). Lung ultrasound examination detected PE with a sensitivity of 90%, specificity of 93%, and with positive and negative predictive values of 85.7 and 95.2%, respectively. Conclusions and Clinical Importance Lung ultrasound examination showed good diagnostic accuracy to identify cardiogenic PE and might be helpful in staging dogs with CVHD. Lung ultrasound examination should be considered as a new, noninvasive diagnostic tool for clinicians managing CVHD in dogs. [ABSTRACT FROM AUTHOR]

Background Three-dimensional (3D) speckle tracking echocardiography ( STE) has been developed to overcome the limitations of two-dimensional (2D) STE and has been applied in the several clinical settings. However, no data exist about the prognostic value of 3D STE-based strain on clinical outcome after myocardial infarction ( MI). This study was designed to investigate the prognostic value of area strain ( AS) by 3D speckle tracking in predicting clinical outcome after acute MI. Methods We assessed 96 patients (62±14 years, 72% male) with acute MI and who had undergone a coronary angiography. Clinical parameters and conventional echocardiographic measurements including the left atrial ( LA) size and tissue Doppler measurements were evaluated. The global left ventricular ( LV) AS was measured using 3D speckle tracking software. The relationship between the AS and clinical outcome of death or hospitalization for heart failure ( HF) was assessed. Results During a median follow-up of 33±10 months, primary endpoint of death or HF occurred in 12 patients (12.5%). AS was predictive of death or HF after adjustment for age, gender, peak CK- MB, LA volume, LV end-systolic volume, LV mass, the ratio of early mitral inflow velocity to early mitral annular velocity, and LV ejection fraction in a multivariate Cox model ( HR 1.23, 95% CI 1.02-1.47, P=.03). In addition, AS added incremental value in predicting death or heart failure on a model based on clinical and standard echocardiographic measures ( P=.008). Conclusion AS is independently associated with increased risk of death or HF after acute MI, suggesting that it can be a useful prognostic parameter in the patients following MI. [ABSTRACT FROM AUTHOR]

Aims To investigate the risk prediction and the risk stratification performances of the Chronic Kidney Disease Epidemiology Collaboration ( CKD- EPI) equation and the Modification of Diet in Renal Disease ( MDRD) equation for estimated glomerular filtration rate ( eGFRCKD- EPI) on heart failure in patients with Type 2 diabetes. Methods The study cohort included 12 258 White and 16 886 African American low-income patients with Type 2 diabetes who were 30-90 years old at baseline. Heart failure risk according to different eGFRMDRD) on heart failure in patients with Type 2 diabetes. Methods The study cohort included 12 258 White and 16 886 African American low-income patients with Type 2 diabetes who were 30-90 years old at baseline. Heart failure risk according to different eGFRCKD- categories was prospectively assessed. Results During a mean follow-up of 6.5 years, 5043 incident heart failure cases were identified. Multivariable-adjusted hazard ratios ( HRs) of heart failure associated with the eGFREPI and eGFRMDRD categories was prospectively assessed. Results During a mean follow-up of 6.5 years, 5043 incident heart failure cases were identified. Multivariable-adjusted hazard ratios ( HRs) of heart failure associated with the eGFRCKD- EPI categories [≥ 90 (reference group), 75-89, 60-74, 30-59 and < 30 ml/min/1.73 m2] were 1.00, 1.11, 1.31, 1.75 and 2.93 ( Ptrend < 0.001) for African American patients, and 1.00, 1.11, 1.08, 1.59 and 2.92 ( Ptrend < 0.001) for White patients, respectively. The model with eGFRCKD- EPI and the other risk factors had significantly higher Harrell's C than the model with eGFRMDRD and other risk factors. Patients reclassified downward from eGFRMDRD showed higher heart failure risk than those who were not reclassified. Conclusions Impaired kidney function (i.e. GFR < 60 ml/min/1.73 mCKD- EPI) estimated by both equations is associated with an increased risk of heart failure. Compared with GFR estimated using the MDRD equation, GFR estimated using the CKD- EPI equation added more predictive power to the model with the other risk factors. Also, eGFRMDRD provided more accurate heart failure risk stratification than eGFRCKD- EPI < 30 ml/min/1.73 m2 showed higher heart failure risk than those who were not reclassified. Conclusions Impaired kidney function (i.e. GFR < 60 ml/min/1.73 m2), and even mildly decreased GFR (60-74 ml/min/1.73 m2) estimated by both equations is associated with an increased risk of heart failure. Compared with GFR estimated using the MDRD equation, GFR estimated using the CKD- EPI equation added more predictive power to the model with the other risk factors. Also, eGFRCKD- EPI provided more accurate heart failure risk stratification than eGFRMDRD . [ABSTRACT FROM AUTHOR]