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Abstract Background Observational studies investigating risk factors in coronavirus disease 2019 (COVID-19) have not considered the confounding effects of advanced care planning, such that a valid picture of risk for elderly, frail and multi-morbid patients is unknown. We aimed to report ceiling of care and cardiopulmonary resuscitation (CPR) decisions and their association with demographic and clinical characteristics as well as outcomes during the COVID-19 pandemic. Methods Retrospective, observational study conducted between 5th March and 7th May 2020 of all hospitalised patients with COVID-19. Ceiling of care and CPR decisions were documented using the Recommended Summary Plan for Emergency Care and Treatment (ReSPECT) process. Unadjusted and multivariable regression analyses were used to determine factors associated with ceiling of care decisions and death during hospitalisation. Results A total of 485 patients were included, of whom 409 (84·3%) had a documented ceiling of care; level one for 208 (50·9%), level two for 75 (18·3%) and level three for 126 (30·8%). CPR decisions were documented for 451 (93·0%) of whom 336 (74·5%) were ‘not for resuscitation’. Advanced age, frailty, White-European ethnicity, a diagnosis of any co-morbidity and receipt of cardiovascular medications were associated with ceiling of care decisions. In a multivariable model only advanced age (odds 0·89, 0·86–0·93 p

Abstract Aims An increasing proportion of patients with heart failure with reduced ejection fraction (HFrEF) have co‐morbidities. The effect of these co‐morbidities on modes of death and the effect of disease‐modifying agents in multi‐morbid patients is unknown. Methods and results We performed a prospective cohort study of ambulatory patients with HFrEF to assess predictors of outcomes. We identified four key co‐morbidities—ischaemic aetiology of heart failure, diabetes mellitus, chronic obstructive pulmonary disease (COPD), and chronic kidney disease (CKD)—that were highly prevalent and associated with an increased risk of all‐cause mortality. We used these data to explore modes of death and the utilization of disease‐modifying agents in patients with and without these co‐morbidities. The cohort included 1789 consecutively recruited patients who had an average age of 69.6 ± 12.5 years, and 1307 (73%) were male. Ischaemic aetiology of heart failure was the most common co‐morbidity, occurring in 1061 (59%) patients; 503 (28%) patients had diabetes mellitus, 283 (16%) had COPD, and 140 (8%) had CKD stage IV/V. During mean follow‐up of 3.8 ± 1.6 years, 737 (41.5%) patients died, classified as progressive heart failure (n = 227, 32%), sudden (n = 112, 16%), and non‐cardiovascular deaths (n = 314, 44%). Multi‐morbid patients were older (P 2.5‐fold and 1.5‐fold increased risk of sudden death, whilst higher doses of beta‐adrenoceptor antagonists were protective (hazard ratio per milligram 0.92, 95% confidence interval 0.86–0.98, P = 0.009). Each milligram of bisoprolol‐equivalent beta‐adrenoceptor antagonist was associated with 9% (P = 0.001) and 11% (P = 0.023) reduction of sudden deaths in patients with

Abstract Chronic heart failure (CHF) is a chronic, progressive disease that has detrimental consequences on a patient's quality of life (QoL). In part due to requirements for market access and licensing, the assessment of current and future treatments focuses on reducing mortality and hospitalizations. Few drugs are available principally for their symptomatic effect despite the fact that most patients' symptoms persist or worsen over time and an acceptance that the survival gains of modern therapies are mitigated by poorly controlled symptoms. Additional contributors to the failure to focus on symptoms could be the result of under‐reporting of symptoms by patients and carers and a reliance on insensitive symptomatic categories in which patients frequently remain despite additional therapies. Hence, formal symptom assessment tools, such as questionnaires, can be useful prompts to encourage more fidelity and reproducibility in the assessment of symptoms. This scoping review explores for the first time the assessment options and management of common symptoms in CHF with a focus on patient‐reported outcome tools. The integration of patient‐reported outcomes for symptom assessment into the routine of a CHF clinic could improve the monitoring of disease progression and QoL, especially following changes in treatment or intervention with a targeted symptom approach expected to improve QoL and patient outcomes.

Background People with chronic heart failure (CHF) experience severe skeletal muscle dysfunction, characterized by mitochondrial abnormalities, which exacerbates the primary symptom of exercise intolerance. However, the molecular triggers and characteristics underlying mitochondrial abnormalities caused by CHF remain poorly understood. Methods and Results We recruited 28 patients with CHF caused by reduced ejection fraction and 9 controls. We simultaneously biopsied skeletal muscle from the pectoralis major in the upper limb and from the vastus lateralis in the lower limb. We phenotyped mitochondrial function in permeabilized myofibers from both sites and followed this by complete RNA sequencing to identify novel molecular abnormalities in CHF skeletal muscle. Patients with CHF presented with upper and lower limb skeletal muscle impairments to mitochondrial function that were of a similar deficit and indicative of a myopathy. Mitochondrial abnormalities were strongly correlated to symptoms. Further RNA sequencing revealed a unique transcriptome signature in CHF skeletal muscle characterized by a novel triad of differentially expressed genes related to deficits in energy metabolism including adenosine monophosphate deaminase 3, pyridine nucleotide‐disulphide oxidoreductase domain 2, and lactate dehydrogenase C. Conclusions Our data suggest an upper and lower limb metabolic myopathy that is characterized by a unique transcriptome signature in skeletal muscle of humans with CHF.

Objective: Estimating survival can aid care planning, but the use of absolute survival projections can be challenging for patients and clinicians to contextualise. We aimed to define how heart failure and its major comorbidities contribute to loss of actuarially predicted life expectancy., Methods: We conducted an observational cohort study of 1794 adults with stable chronic heart failure and reduced left ventricular ejection fraction, recruited from cardiology outpatient departments of four UK hospitals. Data from an 11-year maximum (5-year median) follow-up period (999 deaths) were used to define how heart failure and its major comorbidities impact on survival, relative to an age-sex matched control UK population, using a relative survival framework., Results: After 10 years, mortality in the reference control population was 29%. In people with heart failure, this increased by an additional 37% (95% CI 34% to 40%), equating to an additional 2.2 years of lost life or a 2.4-fold (2.2-2.5) excess loss of life. This excess was greater in men than women (2.4 years (2.2-2.7) vs 1.6 years (1.2-2.0); p<0.001). In patients without major comorbidity, men still experienced excess loss of life, while women experienced less and were non-significantly different from the reference population (1 year (0.6-1.5) vs 0.4 years (-0.3 to 1); p<0.001). Accrual of comorbidity was associated with substantial increases in excess lost life, particularly for diabetes, chronic kidney and lung disease., Conclusions: Comorbidity accounts for the majority of lost life expectancy in people with heart failure. Women, but not men, without comorbidity experience survival close to reference controls., Competing Interests: Competing interests: JG has received a research grant from Medtronic. KKW has received speaker fees from Medtronic, Livanova, St. Jude Medical, Pfizer, Bayer and BMS. MTK has received speaker fees from Merck, Novo Nordisk and unrestricted research awards from Medtronic. ADS has received speaker fees from Abbott, BMS, AstraZeneca, Bayer, Novartis, Boehringer Ingelheim and Servier. VKG has received speaker fees from Abbott and Novartis., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objectives: The aim of the present study was to assess the validity and trending ability of the bioreactance method in estimating cardiac output at rest and in response to stress in advanced heart failure patients and heart transplant candidates., Design: This was a prospective single-center study., Setting: This study was conducted at the heart transplant center at the Freeman Hospital, Newcastle upon Tyne, UK., Participants: Eighteen patients with advanced chronic heart failure due to reduced left ventricular ejection fraction (19 ± 7%), and peak oxygen consumption 12.3 ± 3.9 mL/kg/min., Interventions: Participants underwent right heart catheterization using the Swan-Ganz catheter., Measurements and Main Results: Cardiac output was measured simultaneously using thermodilution and bioreactance at rest and during active straight leg raise test to volitional exertion. There was no significant difference in cardiac index values obtained by the thermodilution and bioreactance methods (2.26 ± 0.59 v 2.38 ± 0.50 L/min, p > 0.05) at rest and peak straight leg raise test (2.92 ± 0.77 v 3.01 ± 0.66 L/min, p > 0.05). In response to active leg raise test, thermodilution cardiac output increased by 22% and bioreactance by 21%. There was also a strong relationship between cardiac outputs from both methods at rest (r = 0.88, p < 0.01) and peak straight leg raise test (r = 0.92, p < 0.01). Cartesian plot analysis showed good trending ability of bioreactance compared with thermodilution (concordance rate = 93%) CONCLUSIONS: `Cardiac output measured by the bioreactance method is comparable to that from the thermodilution method. Bioreactance method may be used in clinical practice to assess hemodynamics and improve management of advanced heart failure patients undergoing heart transplant assessment., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: Long-term right ventricular (RV) pacing leads to heart failure or a decline in left ventricular (LV) function in up to a fifth of patients. We aimed to establish whether patients with focal fibrosis detected on late gadolinium enhancement cardiovascular magnetic resonance (CMR) have deterioration in LV function after RV pacing., Methods: We recruited 84 patients with LV ejection fraction ≥40% into 2 observational CMR studies. Patients (n=34) with a dual-chamber device and preserved atrioventricular conduction underwent CMR in 2 asynchronous pacing modes (atrial asynchronous and dual-chamber asynchronous) to compare intrinsic atrioventricular conduction with forced RV pacing. Patients (n=50) with high-grade atrioventricular block underwent CMR before and 6 months after pacemaker implantation to investigate the medium-term effects of RV pacing., Results: The key findings were (1) initiation of RV pacing in patients with fibrosis, compared with those without, was associated with greater immediate changes in both LV end-systolic volume index (5.3±3.5 versus 2.1±2.4 mL/m 2 ; P <0.01) and LV ejection fraction (-5.7±3.4% versus -3.2±2.6%; P =0.02); (2) medium-term RV pacing in patients with fibrosis, compared with those without, was associated with greater changes in LV end-systolic volume index (8.0±10.4 versus -0.6±7.3 mL/m 2 ; P =0.008) and LV ejection fraction (-12.3±7.9% versus -6.7±6.2%; P =0.012); (3) patients with fibrosis did not experience an improvement in quality of life, biomarkers, or functional class after pacemaker implantation; (4) after 6 months of RV pacing, 10 of 50 (20%) patients developed LV ejection fraction <35% and were eligible for upgrade to cardiac resynchronization according to current guidelines. All 10 patients had fibrosis on their preimplant baseline scan and were identified by >1.1 g of fibrosis with 90% sensitivity and 70% specificity., Conclusions: Fibrosis detected on CMR is associated with immediate- and medium-term deterioration in LV function following RV pacing and could be used to identify those at risk of heart failure before pacemaker implantation.

Objective: The present study assessed agreement between resting cardiac output estimated by inert gas rebreathing (IGR) and thermodilution methods in patients with heart failure and those implanted with a left ventricular assist device (LVAD)., Methods and Results: Hemodynamic measurements were obtained in 42 patients, 22 with chronic heart failure and 20 with implanted continuous flow LVAD (34 males, aged 50 ± 11 years). Measurements were performed at rest using thermodilution and IGR methods. Cardiac output derived by thermodilution and IGR were not significantly different in LVAD (4.4 ± 0.9 L/min vs 4.7 ± 0.8 L/min, P = .27) or patients with heart failure (4.4 ± 1.4 L/min vs 4.5 ± 1.3 L/min, P = .75). There was a strong relationship between thermodilution and IGR cardiac index (r = 0.81, P = .001) and stroke volume index (r = 0.75, P = .001). Bland-Altman analysis showed acceptable limits of agreement for cardiac index derived by thermodilution and IGR, namely, the mean difference (lower and upper limits of agreement) for patients with heart failure -0.002 L/min/m 2 (-0.65 to 0.66 L/min/m 2 ), and -0.14 L/min/m 2 (-0.78 to 0.49 L/min/m 2 ) for patients with LVAD., Conclusions: IGR is a valid method for estimating cardiac output and should be used in clinical practice to complement the evaluation and management of chronic heart failure and patients with an LVAD., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Aims: Heart failure with reduced ejection fraction (HFrEF) induces skeletal muscle mitochondrial abnormalities that contribute to exercise limitation; however, specific mitochondrial therapeutic targets remain poorly established. This study quantified the relationship and contribution of distinct mitochondrial respiratory states to prognostic whole-body measures of exercise limitation in HFrEF., Methods and Results: Male patients with HFrEF (n = 22) were prospectively enrolled and underwent ramp-incremental cycle ergometry cardiopulmonary exercise testing to determine exercise variables including peak pulmonary oxygen uptake (V̇O 2peak ), lactate threshold (V̇O 2LT ), the ventilatory equivalent for carbon dioxide (V̇ E /V̇CO 2LT ), peak circulatory power (CircP peak ), and peak oxygen pulse. Pectoralis major was biopsied for assessment of in situ mitochondrial respiration. All mitochondrial states including complexes I, II, and IV and electron transport system (ETS) capacity correlated with V̇O 2peak (r = 0.40-0.64; P < 0.05), V̇O 2LT (r = 0.52-0.72; P < 0.05), and CircP peak (r = 0.42-0.60; P < 0.05). Multiple regression analysis revealed that combining age, haemoglobin, and left ventricular ejection fraction with ETS capacity could explain 52% of the variability in V̇O 2peak and 80% of the variability in V̇O 2LT , respectively, with ETS capacity (P = 0.04) and complex I (P = 0.01) the only significant contributors in the model., Conclusions: Mitochondrial respiratory states from skeletal muscle biopsies of patients with HFrEF were independently correlated to established non-invasive prognostic cycle ergometry cardiopulmonary exercise testing indices including V̇O 2peak , V̇O 2LT , and CircP peak . When combined with baseline patient characteristics, over 50% of the variability in V̇O 2peak could be explained by the mitochondrial ETS capacity. These data provide optimized mitochondrial targets that may attenuate exercise limitations in HFrEF., (© 2021 The Authors. ESC Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.)

Although left ventricular assist device (LVAD) improves functional capacity, on average LVAD patients are unable to achieve the aerobic capacity of normal healthy subjects or mild heart failure patients. The aim of this study was to examine if markers of right ventricular (RV) function influence maximal exercise capacity. This was a single-center prospective study that enrolled 20 consecutive HeartWare ventricular assist device patients who were admitted at the Freeman Hospital (Newcastle upon Tyne, United Kingdom) for a heart transplant assessment from August 2017 to October 2018. Mean peak oxygen consumption (Peak VO2) was 14.0 ± 5.0 ml/kg/min, and mean peak age and gender-adjusted percent predicted oxygen consumption (%VO2) was 40.0% ± 11.5%. Patients were subdivided into two groups based on the median peak VO2, so each group consisted of 10 patients (50%). Right-sided and pulmonary pressures were consistently higher in the group with poorer exercise tolerance. Patients with poor exercise tolerance (peak VO2 below the median) had higher right atrial pressures at rest (10.6 ± 6.4 vs. 4.3 mmHg ± 3.2; p = 0.02) and the increase with passive leg raising was significantly greater than those with preserved exercise tolerance (peak VO2 above the median). Patients with poor functional capacity also had greater RV dimensions (4.4 cm ± 0.5 vs. 3.7 cm ± 0.5; p = 0.02) and a higher incidence of significant tricuspid regurgitation (moderate or severe tricuspid regurgitation in five patients in the poor exercise capacity group vs. none in the preserved exercise capacity group; p = 0.03). In conclusion, echocardiographic and hemodynamic markers of RV dysfunction discriminate between preserved and nonpreserved exercise capacity in HeartWare ventricular assist device patients., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2020.)

Background: Parents' health-seeking behaviors has changed during the COVID-19 pandemic. Providing parents with guidance in decision making might improve their confidence to seek timely advice when a child becomes ill. The aim of this study was to evaluate the "How to recognize if your child is seriously ill" leaflet on parents' confidence, health-seeking behaviors, and usefulness during the COVID-19 lockdown. Method: A nine-item survey, codesigned with parent advisors, was used to measure confidence and health-seeking behavior. Social media was used for data collection in a 6-week period (April-June 2020) during COVID-19 lockdown in the United Kingdom. Categorical data were analyzed as frequencies, and inductive content analysis was performed with the qualitative data. Results: In total, 171 parents responded. Most parents ( n = 160, 93.6%) found the leaflet helpful. The leaflet increased the confidence among 116 parents (67.8%) to recognize if their child is ill, and 156 (91.2%) parents had a better understanding of when and where to seek help. Thirty-three (19.2%) parents used the leaflet, while their child was unwell during COVID-19 lockdown, and in 14 (42%) cases, the leaflet resulted in changing health-seeking behavior for that episode. Twelve of these parents decided to seek medical consultation when they had not planned to before. Content analysis revealed three categories. (1) Knowledge-parents found the leaflet an objective source to validate their concerns. (2) Usability-parents reported that the leaflet was clearly designed. (3) Decision aid-parents commented that the leaflet provided clarification around recognition of serious symptoms and when and where to seek appropriate care. Conclusions: Our leaflet provided parents with guidance on decision making and risk assessment of ill children during COVID-19 lockdown. Parents found it helpful; it increased their confidence and positively changed their health-seeking behaviors. Providing parents with targeted information to recognize serious illness in children at home could potentially foster self-care and safely maintain a reduction in pediatric emergency attendances for self-limiting illnesses., (Copyright © 2020 Lim, Mistry, Battersby, Dockerty, Koshy, Chopra, Carey and Latour.)

Background: Hospitalization is a common adverse event in people with heart failure and reduced ejection fraction, yet is often not primarily due to decompensated heart failure (HF). We investigated the long-term prognosis following infection-related hospitalization., Methods: We conducted a prospective observational cohort study of 711 people with heart failure and reduced ejection fraction recruited from 4 specialist HF clinics in the United Kingdom. All hospitalization episodes (n=1568) were recorded and categorized as primarily due to decompensated HF, other cardiovascular disease, infection-related, or other noncardiovascular disease. Survival was determined after the first hospitalization., Results: During 2900 patient-years of follow-up, there were a total of 14 686 hospital days. At least one hospitalization occurred in 467 people (66%); 25% of first hospitalizations were primarily due to infection and these were not associated with typical signs including tachycardia and pyrexia. Compared with other categories of hospitalization, infection-related was associated with older age, lower serum albumin, higher blood neutrophil counts, and greater prevalence of chronic obstructive pulmonary disease at recruitment. Median survival after first infection-related hospitalization was 18.6 months, comparable to that after first decompensated HF hospitalization, even after age-sex adjustment. The burden of all-cause rehospitalization was comparable irrespective of the category of first hospitalization, but infection more commonly caused re-hospitalization after index infection hospitalization., Conclusions: Infection is a common driver of hospitalization in heart failure and reduced ejection fraction and often presents without classical signs. It is associated with high mortality rates, comparable to decompensated HF, and a major burden of rehospitalization caused by recurrent episodes of infection.

Background: Patients with coexistent chronic heart failure (CHF) and diabetes mellitus (DM) demonstrate greater exercise limitation and worse prognosis compared with CHF patients without DM, even when corrected for cardiac dysfunction. Understanding the origins of symptoms in this subgroup may facilitate development of targeted treatments. We therefore characterized the skeletal muscle phenotype and its relationship to exercise limitation in patients with diabetic heart failure (D-HF)., Methods: In one of the largest muscle sampling studies in a CHF population, pectoralis major biopsies were taken from age-matched controls (n = 25), DM (n = 10), CHF (n = 52), and D-HF (n = 28) patients. In situ mitochondrial function and reactive oxygen species, fibre morphology, capillarity, and gene expression analyses were performed and correlated to whole-body exercise capacity., Results: Mitochondrial respiration, content, coupling efficiency, and intrinsic function were lower in D-HF patients compared with other groups (P < 0.05). A unique mitochondrial complex I dysfunction was present in D-HF patients only (P < 0.05), which strongly correlated to exercise capacity (R 2 = 0.64; P < 0.001). Mitochondrial impairments in D-HF corresponded to higher levels of mitochondrial reactive oxygen species (P < 0.05) and lower gene expression of anti-oxidative enzyme superoxide dismutase 2 (P < 0.05) and complex I subunit NDUFS1 (P < 0.05). D-HF was also associated with severe fibre atrophy (P < 0.05) and reduced local fibre capillarity (P < 0.05)., Conclusions: Patients with D-HF develop a specific skeletal muscle pathology, characterized by mitochondrial impairments, fibre atrophy, and derangements in the capillary network that are linked to exercise intolerance. These novel preliminary data support skeletal muscle as a potential therapeutic target for treating patients with D-HF., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

We sought to determine hemodynamic mechanisms of exercise intolerance in a group of patients with the HeartWare ventricular assist device (VAD) compared to a group of heart failure patients. Twenty VAD and 22 heart failure patients underwent symptom-limited active straight leg raising exercise during right heart catheterization with thermodilution (TD), and upright cycling cardiopulmonary stress testing with cardiac output measurement by inert gas rebreathing (IGR) method. The TD and IGR exercise cardiac indexes were higher in VAD compared with heart failure group (both P < 0.05), although there was only a borderline increase in peak exercise oxygen consumption (VO2) (P = 0.06). Baseline and exercise right heart catheterization pressures were not significantly different between the two groups. The only significant independent predictors of peak VO2 in the heart failure group were exercise heart rate and cardiac index (both P < 0.05). In contrast, for the VAD group only, resting pulmonary arterial wedge and pulmonary arterial mean pressures were independently related to peak VO2 (both P < 0.05). Thus, in heart failure, exercise cardiac index is an important limitation to exercise capacity, and VADs increase exercise cardiac index. However, in VAD patients, this only produces limited benefits as increased pulmonary and pulmonary wedge pressures limit increases in exercise capacity.

Background: Previous studies in heart failure with reduced ejection fraction (HFrEF) suggest that skeletal muscle mitochondrial impairments are associated with exercise intolerance in men. However, the nature of this relationship in female patients remains to be elucidated. This study aimed to determine the relationship between skeletal muscle mitochondrial impairments and exercise intolerance in male and female patients with HFrEF., Methods: Mitochondrial respiration, enzyme activity, and gene expression were examined in pectoralis major biopsies from age-matched male (n = 45) and female (n = 11) patients with HFrEF and healthy-matched male (n = 24) and female (n = 11) controls. Mitochondrial variables were compared between sex and related to peak exercise capacity., Results: Compared with sex-matched controls, complex I mitochondrial oxygen flux was 17% (P = 0.030) and 29% (P = 0.013) lower in male and female patients with HFrEF, respectively, which correlated to exercise capacity (r = 0.71; P > 0.0001). Female HFrEF patients had a 32% (P = 0.023) lower mitochondrial content compared with controls. However, after adjusting for mitochondrial content, male patients demonstrated lower complex I function by 15% (P = 0.030). Expression of key mitochondrial genes regulating organelle dynamics and maintenance (i.e. optic atrophy 1, peroxisome proliferator-activated receptor γ coactivator-1α, NADH:ubiquinone oxidoreductase core subunit S1/S3, and superoxide dismutase 2) were selectively lower in female HFrEF patients., Conclusions: These data provide novel evidence that HFrEF induces divergent sex-specific mitochondrial phenotypes in skeletal muscle that predispose towards exercise intolerance, impacting mitochondrial 'quantity' in female patients and mitochondrial 'quality' in male patients. Therapeutic strategies to improve exercise tolerance in HFrEF should consider targeting sex-specific mitochondrial abnormalities in skeletal muscle., (© 2019 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of Society on Sarcopenia, Cachexia and Wasting Disorders.)

Introduction : Chronic heart failure is characterized by reduced exercise capacity. Invasive exercise hemodynamics are not routinely performed unless patients undergo transplant or left ventricular assist devices (LVAD) assessment, though now with readily available noninvasive devices, exercise hemodynamics are easily obtained. Our contention is that this is a valuable opportunity to acquire a more accurate measure of cardiac status in heart failure. Exercise hemodynamic measures such as cardiac power output can be carried out cheaply and effectively. Recent studies have highlighted the added value of exercise hemodynamics in prognostication of heart failure, and their role in assessing myocardial recovery in LVADs. Areas covered : In this review, we explore the literature available on Medline until 2019 focusing on resting and exercise hemodynamics alongside the methods of assessment (invasive and noninvasive) in heart failure with reduced ejection fraction and patients with implanted LVADs. Expert opinion : Hemodynamics measured both at rest and exercise are expected to play a significant role in the work up of transplant and LVAD patients. Furthermore, there is the potential to utilize noninvasive assessment in a complimentary fashion to support patient selection and improve the monitoring of response to treatment across the full cohort of heart failure patients.

Aims: The UK National Institute for Health and Care Excellence (UK-NICE) and European Society of Cardiology (ESC) guidelines advise natriuretic peptide (NP) assessment in patients presenting to primary care with symptoms possibly due to chronic heart failure (HF), to determine need for specialist involvement. This prospective service evaluation aimed to describe the diagnostic and prognostic utility of these guidelines., Methods and Results: We prospectively collected clinical, echocardiography and outcomes data (minimum 5 years) from all patients referred to the Leeds HF Service for 12 months of following the initiation of the NP-guideline-directed pathway. Between 1 May 2012 and 1 August 2013, 1020 people with symptoms possibly due to HF attended either with a raised NT-pro-BNP or a previous myocardial infarction (MI) with an overall rate of left ventricular systolic dysfunction (LVSD) of 33%. Of these, 991 satisfied the ESC criteria (NT-pro-BNP ≥125 pg/mL) in whom the rate of LVSD was 32%, and 821 the UK-NICE criteria in whom the rate of LVSD was 49% in those with a previous MI, 25% in those with NT-pro-BNP concentration 400-2000 pg/mL, and 54% in those with NT-pro-BNP concentration of >2000 pg/mL. An NT-pro-BNP concentration 125-400 pg/mL had a 12% risk of LVSD. Specificity was poor in women >70 years, who made up the largest proportion of attendees. Elevated NT-pro-BNP levels were associated with lower survival even in the absence of LVSD., Conclusion: In people referred through the ESC and UK-NICE guidelines, elevated NT-pro-BNP is a marker of increased mortality risk, but there is wide variation in specificity for LVSD. Age- and sex-adjusted criteria might improve performance., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2018. For permissions, please email: journals.permissions@oup.com.)

Introduction: Cardiac magnetic resonance (CMR) imaging has been shown to be safe as an imaging modality for patients with cardiac resynchronization (CRT) devices. As a widely accepted method of measuring cardiac volumes, mass, and ejection fraction, CMR has become a core part of the diagnostic panel. A number of studies have already highlighted a role in optimizing left ventricular lead placemen with evidence that scanning is useful prior to implantation to predict outcomes and optimizing device effect. By balancing the considerations of CMR with the benefits, there may be further applications., Areas Covered: The aim of the review is to discuss the applications of CMR pre and post CRT implantation with an exploration into the future utility of this imaging modality., Expert Opinion: CMR has underutilized potential in improving diagnostics and care for patients implanted with CRT devices. Scanning patients post CRT implantation is not conducted routinely despite multiple potential applications. By employing modern technology and techniques, there is scope to improve CMR utility postimplantation by scanning at higher field strengths whilst CRT is active. We believe CMR has utility with advances expected to translate to improved treatment response and clinical outcomes.

Objectives: Heart rate variability (HRV) and haemodynamic response to exercise (i.e. peak cardiac power output) are strong predictors of mortality in heart failure. The present study assessed the relationship between measures of HRV and peak cardiac power output., Design: In a prospective observational study of 33 patients (age 54 ± 16 years) with chronic heart failure with reduced left ventricular ejection fraction (29 ± 11%), measures of the HRV (i.e. R-R interval and standard deviation of normal R-R intervals, SDNN) were recorded in a supine position. All patients underwent maximal graded cardiopulmonary exercise testing with non-invasive (inert gas rebreathing) cardiac output assessment. Cardiac power output, expressed in watts, was calculated as the product of cardiac output and mean arterial blood pressure., Results: The mean RR and SDNN were 837 ± 166 and 96 ± 29 ms, peak exercise cardiac power output 2.28 ± 0.85 watts, cardiac output 10.34 ± 3.14 L/min, mean arterial blood pressure 98 ± 14 mmHg, stroke volume 91.43 ± 40.77 mL/beat, and oxygen consumption 19.0 ± 5.6 mL/kg/min. There was a significant but only moderate relationship between the RR interval and peak exercise cardiac power output (r = 0.43, p = .013), cardiac output (r = 0.35, p = .047), and mean arterial blood pressure (r = 0.45, p = .009). The SDNN correlated with peak cardiac power output (r = 0.42, p = .016), mean arterial blood arterial (r = 0.41, p = .019), and stroke volume (r = 0.35, p = .043)., Conclusions: Moderate strength of the relationship between measures of HRV and cardiac response to exercise suggests that cardiac autonomic function is not good indicator of overall function and pumping capability of the heart in chronic heart failure.

Background: The Surprise Question: 'would you be surprised if this patient were to die within the next year?' has been shown to predict mortality in patients with chronic kidney disease and cancer. This prospective study aimed to determine whether the Surprise Question could identify heart failure patients with a prognosis of less than 1 year, and whether the Surprise Question can be used by different healthcare professionals., Methods and Results: Overall, 129 consecutive patients admitted with decompensated heart failure were included. Doctors and nurses were asked to provide a 'surprised' or 'not surprised' response to the Surprise Question for each patient. Patients were followed up until death or 1 year following study inclusion. The sensitivity, specificity, positive predictive value and negative predictive value of the Surprise Question were assessed. Cox regression was used to determine covariates significantly associated with survival. The Surprise Question showed excellent sensitivity (0.85) and negative predictive value (0.88) but only fair specificity (0.59) and positive predictive value (0.52) when asked of cardiologists. There were similar levels of accuracy between doctors and specialist nurses. The Surprise Question was significantly associated with all-cause mortality in multivariate regression analysis (hazard ratio 2.8, 95% confidence interval 1.0-7.9, P = 0.046)., Conclusion: This study demonstrates that the Surprise Question can identify heart failure patients within the last year of life. Despite over-classification of patients into the 'not surprised' category, the Surprise Question identified nearly all patients who were within the last year of life, whilst also accurately identifying those unlikely to die., (© 2018 The Authors. European Journal of Heart Failure © 2018 European Society of Cardiology.)

Background The CASTLE - AF (Catheter Ablation versus Standard Conventional Therapy in Patients With Left Ventricular Dysfunction and Atrial Fibrillation) trial recently reported that catheter ablation of atrial fibrillation ( AF ) improves survival in heart failure (HF) with reduced ejection fraction ( HF r EF ). However, established AF was not associated with mortality in trials of contemporary HF r EF pharmacotherapies. We investigated whether HF r EF pathogenesis may influence the conclusions of studies evaluating the prognostic impact of AF . Methods and Results Using a prospective cohort study of 791 patients with HFr EF , with AF determined using 24-hour ambulatory ECG monitoring, univariable and multivariable Cox regression analyses were used to define the association between AF and mode-specific mortality (mean follow-up of 5.4 years). One-year HF-related hospitalization was assessed with binary logistic regression analysis. One-year cardiac remodeling was assessed in a subgroup (n=378) using echocardiography. AF was present in 28.2% of patients, with 9.4% of these being paroxysmal. While AF was associated with increased risk of all-cause mortality (hazard ratio, 1.27; 95% confidence interval 1.03-1.57), with diverging survival curves after 1 year of follow-up, this association was lost in age-sex-adjusted analyses. However, AF was associated with increased risk of age-sex-adjusted all-cause mortality in people with ischemic pathogenesis, with a statistically significant interaction between pathogenesis and AF. This was predominantly attributed to progressive HF deaths. After 1 year, HF hospitalization and cardiac remodeling were not associated with AF , even in people with ischemic pathogenesis. Conclusions AF is associated with increased risk of death in HF r EF of ischemic pathogenesis, predominantly due to progressive HF deaths during long-term follow-up. HF r EF pathogenesis should be considered in trial design and interpretation.

Objective: Chronic heart failure is characterised by reduced exercise tolerance. We assessed the effects of different fractions of inspired oxygen (FiO2) on exercise capacity using cycle ergometry to see if there is a dose-response relationship between FiO2 and exercise performance., Methods: This was a single-centre, randomised, single-blinded, cross-over study. Thirty-one patients with chronic heart failure undertook three maximal incremental exercise tests. For each test, a different FiO2 was used: room air (20.9%), 28% or 40%. The patient had to breathe in via a venturi mask allowing the investigator to control the FiO2 and maintain the patient's blinding. The three tests were carried out in random order with a minimum of 4 days' rest between any two tests., Results: Exercise time increased from (mean±standard deviations) 501±24.9 s on room air to 525±25.1 s (p=0.042) and 536±24.2 (p<0.001) seconds, with FiO2 of 28% and 40%, respectively. Maximal metabolic equivalents were 3.47±0.16 on room air and 3.67±0.16 (p=0.002) and 3.70±0.15 (p<0.001) on 28% and 40% oxygen, respectively. Maximal workload was 78.4±4.5 W on room air and 82.6±4.3 (p=0.021) and 84.2±4.2 (p=0.005) on 28% and 40% oxygen, respectively. Increasing FiO2 resulted in higher mean oxygen saturations during exercise. The mean heart rate during exercise was lower with FiO2 of 28% with no further drop at 40%. Changing FiO2 had no effect on blood pressure., Conclusions: Increasing FiO2 to 28% or 40% acutely improves exercise capacity in patients with chronic heart failure., Trial Registration Number: Eudract number: 2014-003380-38; Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: Primary percutaneous coronary intervention (PPCI) for ST-segment elevation myocardial infarction (STEMI) is a therapeutic success when supported by dual antiplatelet therapy. Prasugrel has been introduced as a potential alternative to clopidogrel alongside aspirin. We aimed to assess prasugrel versus clopidogrel mortality outcomes in patients admitted with STEMI undergoing PPCI., Methods: Retrospective analysis of prospectively collected data of 1688 consecutive STEMI patients undergoing PPCI at a regional tertiary centre. Patients with age ≥75 years, weight<60 kg or history of cerebrovascular accident or TIA's, active bleeding or known hepatic impairment were excluded. All patients from March 2008 to 16 December 2009 belong to the Clopidogrel group and from 17 December 2009 to June 2011 belong to the Prasugrel group., Results: A total of 866 patients were in the Clopidogrel group and 822 patients in the prasugrel group. In-hospital mortality was 1.7% in the Clopidogrel and 1.5% in Prasugrel group (P = 0.40). 30-day postdischarge mortality was 2.4% and 1.8% (P = 0.25) in the Clopidogrel and Prasugrel group, respectively. One-year mortality rate was recorded in 62 patients (3.7%): 39 (4.5%) in the Clopidogrel group and 23 (2.8%) in the prasugrel group. In the Cox proportional hazard model, the adjusted hazard ratio for all-cause mortality for the prasugrel group was 0.47 (95% CI: 0.253-0.881; P = 0.018). Independent predictors of one-year mortality postdischarge were age, admission creatinine and haemoglobin, admission heart rate, total ischaemic time, the presence of multivessel coronary artery disease, previous MI and post-PCI TIMI flow., Conclusion: In PPCI-treated STEMI patients, prasugrel is associated with a significant reduction in one-year mortality compared with clopidogrel., (© 2013 John Wiley & Sons Ltd.)