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Atherosclerosis is a chronic inflammatory disease driven by macrophage accumulation in medium and large sized arteries. Macrophage polarization and inflammation are governed by microRNAs (miR) that regulate the expression of inflammatory proteins and cholesterol trafficking. Previous transcriptomic analysis led us to hypothesize that miR-155-5p (miR-155) is regulated by conjugated linoleic acid (CLA), a pro-resolving mediator which induces regression of atherosclerosis . In parallel, as extracellular vesicles (EVs) and their miR content have potential as biomarkers, we investigated alterations in urinary-derived EVs (uEVs) during the progression of human coronary artery disease (CAD). miR-155 expression was quantified in aortae from ApoE mice fed a 1% cholesterol diet supplemented with CLA blend (80:20, -9, -11: -10, -12 respectively) which had been previously been shown to induce atherosclerosis regression. In parallel, human polarized THP-1 macrophages were used to investigate the effects of CLA blend on miR-155 expression. A miR-155 mimic was used to investigate its inflammatory effects on macrophages and on human carotid endarterectomy (CEA) plaque specimens (n = 5). Surface marker expression and miR content were analyzed in urinary extracellular vesicles (uEVs) obtained from patients diagnosed with unstable (n = 12) and stable (n = 12) CAD. Here, we report that the 1% cholesterol diet increased miR-155 expression while CLA blend supplementation decreased miR-155 expression in the aorta during atherosclerosis regression . CLA blend also decreased miR-155 expression in human THP-1 polarized macrophages. Furthermore, in THP-1 macrophages, miR-155 mimic decreased the anti-inflammatory signaling proteins, BCL-6 and phosphorylated-STAT-3. In addition, miR-155 mimic downregulated BCL-6 in CEA plaque specimens. uEVs from patients with unstable CAD had increased expression of miR-155 in comparison to patients with stable CAD. While the overall concentration of uEVs was decreased in patients with unstable CAD, levels of CD45+ uEVs were increased. Additionally, patients with unstable CAD had increased CD11b+ uEVs and decreased CD16+ uEVs. miR-155 suppresses anti-inflammatory signaling in macrophages, is decreased during regression of atherosclerosis and is increased in uEVs from patients with unstable CAD suggesting miR-155 has potential as a prognostic indicator and a therapeutic target.

Aims Implantable pulmonary artery pressure (PAP) sensors have been shown to reduce heart failure hospitalizations (HFH) in selected patients. The goal of this study was to evaluate the safety and efficacy of a novel wireless PAP monitoring system in patients with heart failure (HF). Methods and results This is a prospective, multi‐centre, open‐label, single‐arm trial evaluating the safety and efficacy of the Cordella™ PA Sensor System including the comprehensive Cordella™ Heart Failure System (CHFS) in patients with New York Heart Association (NYHA) Class III heart failure with a heart failure hospitalization and/or increase of N‐terminal pro‐Brain Natriuretic Peptide (NT‐proBNP) within 12 months of enrolment. The primary efficacy endpoint was the accuracy of PA sensor mean PAP measurements, compared with fluid‐filled catheter mean PAP measurements obtained by standard right heart catheterization (RHC) at 90 days post‐implant, assessed in all patients with a successful implant. The primary safety endpoint was freedom from adverse events associated with use of the Cordella PA Sensor System through 30 days post‐implant, assessed in all patients who entered the cath lab for PA sensor implant. The PA sensor was successfully implanted in 70 patients. Equivalence between the PA sensor and RHC for mean pulmonary artery pressures was excellent with measurements confined within the equivalence bounds of −4.0 to 4.0 mmHg (mean PAP: 0.0 to 2.9 mmHg, P = 0.003). The device safety profile was excellent with 98.6% freedom from Device System Related Complications, defined as invasive treatment, device explant or death. There were no pressure sensor failures. Patients' adherence to daily measurement transmissions of PAP and vital signs was 94%. Conclusions This trial supports the safety and efficacy of the Cordella PA Sensor System and in conjunction with the CHFS enables comprehensive HF management in NYHA class III heart failure patients.

Aims Many European healthcare providers struggle to adopt multidisciplinary, integrated care pathways for people with heart failure (HF) as recommended by the European Society of Cardiology. PRO‐HF (Program to Optimize Heart Failure Patient Pathways) was developed to help clinicians identify strengths, gaps, and shortcomings in their HF pathways and support tailored interventions to optimize pathways and enhance patient care. We report initial findings from baseline assessments of HF pathway characteristics and challenges from 10 hospitals in six European countries (France, Ireland, Portugal, Spain, The Netherlands, and United Kingdom). Methods and results Baseline assessments were holistic appraisals of full HF services to calibrate current status and development needs and assist management teams in prioritizing improvement projects. Assessments were performed using a comprehensive checklist of measures covering the HF patient journey from diagnosis to ongoing follow‐up. These included a digital survey sent to full HF care teams and one‐to‐one interviews. The digital survey focused on four key areas (HF outpatient clinic; remote patient management; efficient device implantation and inpatient pathways; and network maximization) and 16 dimensions of excellence. Priority areas and themes for action identified in baseline assessments were (i) provision of HF specialist care; (ii) data capture and analysis; (iii) institutional care protocols; (iv) hospital‐wide strategies; and (v) multidisciplinary teams (MDTs). Suboptimal specialist care of emergency inpatients was an issue at all hospitals and prioritized at 8/10. Availability and accessibility of data on patients, activities, and outcomes was an issue at all hospitals and prioritized by 4/10. A lack of clear protocols, templates, and tools for some HF activities created variability in patient care (e.g., HF specialist consultations, diagnostic testing, follow‐up appointments, medications, and device eligibility) and inefficient use of clinician time. This made it difficult to initiate new technologies (e.g., remote patient monitoring) due to the risk of overburdening staff. MDTs were frequently understaffed. Multiple interventions were identified to address gaps and shortcomings that could be tailored to specific needs of individual hospitals (e.g., inpatient pathway optimization, creation/optimization of HF outpatient clinics, development of an HF performance dashboard, enhancement of protocol adherence, streamlining cardiac resynchronisation therapy pathways, and MDT coordination). Conclusions PRO‐HF provides a valuable opportunity to identify gaps and significant shortcomings in HF pathways in European hospitals. Preliminary findings from hospitals that have initiated suggested changes to address these challenges are encouraging, though longer‐term follow‐up from more hospitals is needed to confirm the impact of PRO‐HF on HF pathway optimization and patient care.

Aims In the SIRONA 2 trial, the safety and efficacy of pulmonary artery (PA) pressure (PAP)‐guided heart failure (HF) management using a novel PAP sensor were assessed at 30 and 90 days, respectively, and both endpoints were met. The current study examines the prespecified secondary endpoints of safety and accuracy of the PA sensor along with HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance through 12 months. Methods and results SIRONA 2 is a prospective, multi‐centre, open‐label, single‐arm trial evaluating the Cordella™ PA Sensor System in 70 patients with New York Heart Association (NYHA) functional class III HF with a prior HF hospitalization and/or increase of N‐terminal pro‐brain natriuretic peptide within 12 months of enrolment. Sensor accuracy was assessed and compared with measurements obtained by standard right heart catheterization (RHC). Safety was defined as freedom from prespecified adverse events associated with use of the Cordella PA Sensor System and was assessed in all patients who entered the cath lab for PA sensor implant. HF hospitalizations and mortality, HF symptoms, functional capacity, quality of life, and patient compliance were also assessed. At 12 months, there was good agreement between the Cordella PA Sensor System and RHC, with the average difference for mean PAP being 2.9 ± 7.3 mmHg. The device safety profile was excellent with 98.4% freedom from device/system‐related complications. There were no pressure sensor failures. HF hospitalizations and mortality were low with a rate of 0.33 event per patient year. Symptoms as assessed by NYHA (P < 0.0001) and functional capacity as measured by 6 min walk test (P = 0.02) were significantly improved. Patients' adherence to daily transmissions of PAP and vital signs measurements was 95%. Conclusions Long‐term follow‐up of the SIRONA 2 trial supports the safety and accuracy of the Cordella PA Sensor System in enabling comprehensive HF management in NYHA class III HF patients.

Aims: To determine if newer criteria for diagnosing and staging acute kidney injury (AKI) during heart failure (HF) admission are more predictive of clinical outcomes at 30 days and 1 year than the traditional worsening renal function (WRF) definition. Methods: We analyzed prospectively collected clinical data on 637 HF admissions with 30-day and 1-year follow-up. The incidence, stages, and outcomes of AKI were determined using the following four definitions: KDIGO, RIFLE, AKIN, and WRF (serum creatinine rise ≥0.3 mg/dl). Receiver operating curves were used to compare the predictive ability of each AKI definition for the occurrence of adverse outcomes (death, rehospitalization, dialysis). Results: AKI by any definition occurred in 38.3% (244/637) of cases and was associated with an increased incidence of 30-day (32.3 vs. 6.9%, χ 2 = 70.1; p < 0.001) and 1-year adverse outcomes (67.5 vs. 31.0%, χ 2 = 81.4; p < 0.001). Most importantly, there was a stepwise increase in primary outcome with increasing stages of AKI severity using RIFLE, KDIGO, or AKIN (p < 0.001). In direct comparison, there were only small differences in predictive abilities between RIFLE and KDIGO and WRF concerning clinical outcomes at 30 days (AUC 0.76 and 0.74 vs. 0.72, χ 2 = 5.6; p = 0.02) as well as for KDIGO and WRF at 1 year (AUC 0.67 vs. 0.65, χ 2 = 4.8; p = 0.03). Conclusion: During admission for HF, the benefits of using newer AKI classification systems (RIFLE, AKIN, KDIGO) lie with the ability to identify those patients with more severe degrees of AKI who will go on to experience adverse events at 30 days and 1 year. The differences in terms of predictive abilities were only marginal.

Background Ebsteins anomaly accounts for less than 1% of all congenital cardiac defects. Whilst typically characterised by dysfunction and anatomical defects of the right ventricle and tricuspid valve, it often co-exists with other congenital defects. Less frequently outflow tract obstruction may arise with associated haemodynamic effects and symptoms. In particular there are few reports in the literature of left ventricular outflow tract obstruction. We believe this is because symptomatic outflow tract obstruction as the presenting complaint of this condition is exceptionally rare. Case presentation We report on a 17 year old male who was referred to the general cardiology clinic with symptoms of exertional fatigue and breathlessness. Transthoracic echocardiogram performed as part of the workup led to the diagnosis of Ebstein’s anomaly. In addition to the characteristic features of this congenital abnormality there was significant dilatation of the right atrium with resultant leftward bulging of the intraventricular septum. The anterior mitral valve leaflet was noted to be elongated with accessory chordal apparatus and demonstrated systolic anterior motion. Turbulence was noted in the left ventricular outflow tract leading to a degree of obstruction. Here we discuss the aetiology and mechanisms behind this unusual presentation. Discussion Ebstein’s anomaly arises due to chromosomal rearrangements affecting early morphogenesis of the right ventricle and tricuspid valve. Associations with other congenital defects such as interatrial communications are well documented. Less commonly the structural abnormalities of this condition lead to functional outflow tract obstruction. Whilst cases have previously described right ventricular outflow tract obstruction there are fewer reports of left ventricular outflow tract obstruction in this patient group. The structural defects that result in dilatation of the right atrium and the atrialised portion of the right ventricle can lead to leftward bulging of the interatrial septum. Turbulence can occur in the left ventricular outflow tract with resultant systolic anterior motion of the mitral valve in a mechanism similar to that encountered in hypertrophic cardiomyopathy. This may only become haemodynamically relevant during exertion. Conclusion In the absence of ventricular dysfunction, arrhythmias or syncope we suggest that it is reasonable to adopt an observational strategy to the management of these patients.

Patients with chronic heart failure (CHF) have symptoms and concerns which are inadequately addressed. Patient-reported outcome measures (PROMs) can potentially improve the identification and management of advanced symptoms and palliative concerns. However, these have not been used in CHF.

•Prompt initiation of diuretic therapy was not correlated with faster decongestion in acute heart failure.•The timing of decongestion but not diuretics was associated with better biomarker trajectories.•Residual congestion rather than the timing of decongestion or diuretics predicted prognosis. Prompt treatment may mitigate the adverse effects of congestion in the early phase of heart failure (HF) hospitalization, which may lead to improved outcomes. We analyzed 814 acute HF patients for the relationships between time to first intravenous loop diuretics, changes in biomarkers of congestion and multiorgan dysfunction, and 1-year composite end point of death or HF hospitalization. B-type natriuretic peptide (BNP), high sensitivity cardiac troponin I (hscTnI), urine and serum neutrophil gelatinase–associated lipocalin, and galectin 3 were measured at hospital admission, hospital day 1, 2, 3 and discharge. Time to diuretics was not correlated with the timing of decongestion defined as BNP decrease ≥ 30% compared with admission. Earlier BNP decreases but not time to diuretics were associated with earlier and greater decreases in hscTnI and urine neutrophil gelatinase–associated lipocalin, and lower incidence of the composite end point. After adjustment for confounders, only no BNP decrease at discharge was significantly associated with mortality but not the composite end point (p = 0.006 and p = 0.062, respectively). In conclusion, earlier time to decongestion but not the time to diuretics was associated with better biomarker trajectories. Residual congestion at discharge rather than the timing of decongestion predicted a worse prognosis.

Background Family-based cardiac screening programmes for persons at risk for genetic cardiac diseases are now recommended. However, the psychological wellbeing and health related quality of life (QoL) of such screened patients is poorly understood, especially in younger patients. We sought to examine wellbeing and QoL in a representative group of adults aged 16 and over in a dedicated family cardiac screening clinic. Methods Prospective survey of consecutive consenting patients attending a cardiac screening clinic, over a 12 month period. Data were collected using two health measurement tools: the Short Form 12 (version 2) and the Hospital Anxiety and Depression Scale (HADS), along with baseline demographic and screening visit-related data. The HADS and SF-12v.2 outcomes were compared by age group. Associations with a higher HADS score were examined using logistic regression, with multi-level modelling used to account for the family-based structure of the data. Results There was a study response rate of 86.6%, with n=334 patients providing valid HADS data (valid response rate 79.5%), and data on n=316 retained for analysis. One-fifth of patients were aged under 25 (n=61). Younger patients were less likely than older to describe significant depression on their HADS scale (p<0.0001), although there were overall no difference between the prevalence of a significant HADS score between the younger and older age groups (18.0% vs 20.0%, p=0.73). Significant positive associates of a higher HADS score were having lower educational attainment, being single or separated, and being closely related to the family proband. Between-family variance in anxiety and depression scores was greater than within-family variance. Conclusions High levels of anxiety were seen amongst patients attending a family-based cardiac screening clinic.Younger patients also had high rates of clinically significant anxiety. Higher levels of anxiety and depression tends to run in families, and this has implications for family screening and intervention programmes.

A previous study suggested that severe left-ventricular hypertrophy (maximum wall thickness ⩾30 mm) in patients with hypertrophic cardiomyopathy is associated with a risk of sudden cardiac death sufficient to warrant consideration for implantation of a cardioverter defibrillator (ICD). However, the prognostic significance of left-ventricular hypertrophy in relation to other clinical risk factors is poorly characterised. We studied 630 patients consecutively referred to one hospital in London, UK (mean age 37 years [SD 16]; 382 male; mean follow-up 59 months). Patients underwent two dimensional and doppler echocardiography, upright exercise testing, and Holter monitoring. 39 patients died suddenly or had an appropriate ICD discharge; nine died from progressive heart failure; 11 from other cardiovascular causes and 23 from non-cardiac causes. There was a trend towards higher probability of sudden death or ICD discharge with increasing wall thickness (p=0·029, relative risk per 5 mm increment 1·31 [95% CI 1·03–1·66]). Of the 39 patients who died suddenly or had an ICD discharge, ten had a wall thickness of 30 mm or more. Patients with wall thickness of 30 mm or more had higher probability of sudden death or ICD discharge than patients with wall thickness less than 30 mm (p=0·049, 2·07 [1·00–4·25]. When considered together, the number of additional risk factors (one to three) was a better predictor of risk of sudden death or ICD discharge than wall thickness (p=0·0001, relative risk per additional factor 2·00 [1·43–2·79] vs p=0·058, 1·26 per 5 mm increment [0·99–1·60]). There was no relation between the pattern of hypertrophy and survival. The risk of sudden death associated with a wall thickness of 30 mm or more in patients without other risk factors is insufficient to justify aggressive prophylactic therapy. Most sudden deaths occurred in patients with wall thickness less than 30 mm, so the presence of mild hypertrophy cannot be used to reassure patients that they are at low risk.