Staphylococcus aureus endocarditis associated with injecting new psychoactive substances.

BACKGROUND: Staphylococcus aureus infective endocarditis (IE) associated with injection of new psychoactive substances (NPS) in Edinburgh from 2014 to 2016 was observed. We compared these infections with a series of S. aureus IE cases in a non-injecting population within Edinburgh. METHODS: NPS-associated S. aureus IE diagnosed between 1 January 2014 and 31 May 2016 in persons who inject drugs (PWID) were compared with a series of S. aureus IE cases from non-PWID. RESULTS: There was a fourfold increase in the annual incidence of S. aureus IE, mainly due to NPS use in PWID. A larger vegetation diameter was seen on echocardiogram in PWID vs non-PWID (median 1.7 cm vs 0.65 cm; p = 0.009) with more embolic complications in PWID (15 PWID vs 1 non-PWID; p = 2.1 x 10-7) but no difference in 90-day mortality (2 PWID vs 4 non-PWID; p = 0.39). CONCLUSIONS: NPS-associated S. aureus IE correlated with complications, such as deep organ embolic abscesses, that were different from non-PWID S. aureus IE. The alarming increase in incidence resolved with targeted public health and legislative measures.

Early-life glucocorticoids programme behaviour and metabolism in adulthood in zebrafish.

Glucocorticoids (GCs) in utero influence embryonic development with consequent programmed effects on adult physiology and pathophysiology and altered susceptibility to cardiovascular disease. However, in viviparous species, studies of these processes are compromised by secondary maternal influences. The zebrafish, being fertilised externally, avoids this problem and has been used here to investigate the effects of transient alterations in GC activity during early development. Embryonic fish were treated either with dexamethasone (a synthetic GC), an antisense GC receptor (GR) morpholino (GR Mo), or hypoxia for the first 120h post fertilisation (hpf); responses were measured during embryonic treatment or later, post treatment, in adults. All treatments reduced cortisol levels in embryonic fish to similar levels. However, morpholino- and hypoxia-treated embryos showed delayed physical development (slower hatching and straightening of head-trunk angle, shorter body length), less locomotor activity, reduced tactile responses and anxiogenic activity. In contrast, dexamethasone-treated embryos showed advanced development and thigmotaxis but no change in locomotor activity or tactile responses. Gene expression changes were consistent with increased (dexamethasone) and decreased (hypoxia, GR Mo) GC activity. In adults, stressed cortisol values were increased with dexamethasone and decreased by GR Mo and hypoxia pre-treatments. Other responses were similarly differentially affected. In three separate tests of behaviour, dexamethasone-programmed fish appeared 'bolder' than matched controls, whereas Mo and hypoxia pre-treated fish were unaffected or more reserved. Similarly, the dexamethasone group but not the Mo or hypoxia groups were heavier, longer and had a greater girth than controls. Hyperglycaemia and expression of GC responsive gene (pepck) were also increased in the dexamethasone group. We conclude that GC activity controls many aspects of early-life growth and development in the zebrafish and that, like other species, manipulating GC status pharmacologically, physiologically or genetically in early life leads to programmable metabolic and behavioural traits in adulthood.

Early-life perturbations in glucocorticoid activity impacts on the structure, function and molecular composition of the adult zebrafish (Danio rerio) heart.

BACKGROUND: Transient early-life perturbations in glucocorticoids (GC) are linked with cardiovascular disease risk in later life. Here the impact of early life manipulations of GC on adult heart structure, function and gene expression were assessed. METHODS AND RESULTS: Zebrafish embryos were incubated in dexamethasone (Dex) or injected with targeted glucocorticoid receptor (GR) morpholino knockdown (GR Mo) over the first 120 h post fertilisation (hpf); surviving embryos (>90%) were maintained until adulthood under normal conditions. Cardiac function, heart histology and cardiac genes were assessed in embryonic (120 hpf) and adult (120 days post fertilisation (dpf)) hearts. GR Mo embryos (120 hpf) had smaller hearts with fewer cardiomyocytes, less mature striation pattern, reduced cardiac function and reduced levels of vmhc and igf mRNA compared with controls. GR Mo adult hearts were smaller with diminished trabecular network pattern, reduced expression of vmhc and altered echocardiographic Doppler flow compared to controls. Dex embryos had larger hearts at 120 hpf (Dex 107.2 ± 3.1 vs. controls 90.2 ± 1.1 µm, p < 0.001) with a more mature trabecular network and larger cardiomyocytes (1.62 ± 0.13 cells/µm vs control 2.18 ± 0.13 cells/µm, p < 0.05) and enhanced cardiac performance compared to controls. Adult hearts were larger (1.02 ± 0.07 µg/mg vs controls 0.63 ± 0.06 µg/mg, p = 0.0007), had increased vmhc and gr mRNA levels. CONCLUSION: Perturbations in GR activity during embryonic development results in short and long-term alterations in the heart.

Future care planning: a first step to palliative care for all patients with advanced heart disease.

Palliative care is recommended for patients with end-stage heart failure with several recent, randomised trials showing improvements in symptoms and quality of life and more studies underway. Future care planning provides a framework for discussing a range of palliative care problems with patients and their families. This approach can be introduced at any time during the patient's journey of care and ideally well in advance of end-of-life care. Future care planning is applicable to a wide range of patients with advanced heart disease and could be delivered systematically by cardiology teams at the time of an unplanned hospital admission, akin to cardiac rehabilitation for myocardial infarction. Integrating cardiology care and palliative care can benefit many patients with advanced heart disease at increased risk of death or hospitalisation. Larger, randomised trials are needed to assess the impact on patient outcomes and experiences.

Potential costs of B-type natriuretic peptide for the identification of people with heart failure in primary care in Scotland - a pilot study.

BACKGROUND AND AIMS: The utility of B-type natriuretic peptide as a screening test for heart failure has been proven in a number of clinical trials. The aims of this study were to assess the utility of the measurement of B-type natriuretic peptide in a 'real life' setting and to estimate the potential costs of implementing its use in primary care in Scotland. METHODS AND RESULTS: Eight general practitioner practices with a combined population of approximately 62,000 were invited to participate. During the 9-month study period, 82 samples for B-type natriuretic peptide measurement were requested. The negative predictive value for B-type natriuretic peptide was 96.9%. Compared with electrocardiography, B-type natriuretic peptide reduced the need for echocardiography by 308 tests per million population per year. The estimated cost of implementation in Scotland is approximately £220,000 per annum, equating to £64.93 per patient correctly diagnosed with heart failure, with a potential saving in echocardiography of £110,800. CONCLUSION: In this pilot study, measurement of plasma B-type natriuretic peptide in a 'real life' setting in primary care had a similar sensitivity, specificity and negative predictive value to that observed in trial populations. B-type natriuretic peptide aids early diagnosis of heart failure in primary care and may help to facilitate prompt introduction of evidence based therapies to modify patient outcomes. The costs of measuring plasma B-type natriuretic peptide in suspected cases of heart failure are modest, and its use would increase the diagnostic capacity of primary care if supported by local cardiology services.

Physiological roles of glucocorticoids during early embryonic development of the zebrafish (Danio rerio).

While glucocorticoids (GCs) are known to be present in the zebrafish embryo, little is known about their physiological roles at this stage. We hypothesised that GCs play key roles in stress response, hatching and swim activity during early development. To test this, whole embryo cortisol (WEC) and corticosteroid-related genes were measured in embryos from 6 to 120 h post fertilisation (hpf) by enzyme linked immunosorbent assay (ELISA) and quantitative real-time polymerase chain reaction (qRT-PCR). Stress response was assessed by change in WEC following stirring, hypoxia or brief electrical impulses applied to the bathing water. The impact of pharmacological and molecular GC manipulation on the stress response, spontaneous hatching and swim activity at different stages of development was also assessed. WEC levels demonstrated a biphasic pattern during development with a decrease from 0 to 36 hpf followed by a progressive increase towards 120 hpf. This was accompanied by a significant and sustained increase in the expression of genes encoding cyp11b1 (GC biosynthesis), hsd11b2 (GC metabolism) and gr (GC receptor) from 48 to 120 hpf. Metyrapone (Met), an inhibitor of 11ß-hydroxylase (encoded by cyp11b1), and cyp11b1 morpholino (Mo) knockdown significantly reduced basal and stress-induced WEC levels at 72 and 120 hpf but not at 24 hpf. Spontaneous hatching and swim activity were significantly affected by manipulation of GC action from approximately 48 hpf onwards. We have identified a number of key roles of GCs in zebrafish embryos contributing to adaptive physiological responses under adverse conditions. The ability to alter GC action in the zebrafish embryo also highlights its potential value for GC research.

Patient Reported Experience Measures (PREMs) in chronic heart failure.

BACKGROUND: Patient Reported Experience Measures (PREMs) is an essential tool for assessing the quality of chronic disease management. The optimal method for delivering a PREMs survey however is unknown. This study reports two methods for assessing PREMs in patients with chronic heart failure (CHF). METHODS: A bespoke online and postal survey delivered to community-based CHF patients in Scotland. RESULTS: A total of 121 patients (73 postal and 48 online) completed the survey. The online cohort were younger, had less contact with a CHF nurse, were more likely to see a CHF doctor and seemed less satisfied with the quality of clinical services. The postal cohort returned fewer negative comments (20 [27.4%] vs 28 [58.3%]; p<0.0001). Several recurring themes were identified. CONCLUSIONS: There are differences in participation rates and responses between postal and online surveys; the accuracy of the feedback gathered using these methods is therefore difficult to determine. Clinicians should consider offering a range of options to enable patients to reflect and 'voice' their opinions regarding clinical services.

Acute cardiovascular effects of apelin in humans: potential role in patients with chronic heart failure.

BACKGROUND: Apelin, the endogenous ligand for the novel G protein-coupled receptor APJ, has major cardiovascular effects in preclinical models. The study objectives were to establish the effects of acute apelin administration on peripheral, cardiac, and systemic hemodynamic variables in healthy volunteers and patients with heart failure. METHODS AND RESULTS: Eighteen patients with New York Heart Association class II to III chronic heart failure, 6 patients undergoing diagnostic coronary angiography, and 26 healthy volunteers participated in a series of randomized, double-blind, placebo-controlled studies. Measurements of forearm blood flow, coronary blood flow, left ventricular pressure, and cardiac output were made by venous occlusion plethysmography, Doppler flow wire and quantitative coronary angiography, pressure wire, and thoracic bioimpedance, respectively. Intrabrachial infusions of (Pyr(1))apelin-13, acetylcholine, and sodium nitroprusside caused forearm vasodilatation in patients and control subjects (all P<0.0001). Vasodilatation to acetylcholine (P=0.01) but not apelin (P=0.3) or sodium nitroprusside (P=0.9) was attenuated in patients with heart failure. Intracoronary bolus of apelin-36 increased coronary blood flow and the maximum rate of rise in left ventricular pressure and reduced peak and end-diastolic left ventricular pressures (all P<0.05). Systemic infusions of (Pyr(1))apelin-13 (30 to 300 nmol/min) increased cardiac index and lowered mean arterial pressure and peripheral vascular resistance in patients and healthy control subjects (all P<0.01) but increased heart rate only in control subjects (P<0.01). CONCLUSIONS: Acute apelin administration in humans causes peripheral and coronary vasodilatation and increases cardiac output. APJ agonism represents a novel potential therapeutic target for patients with heart failure.

Life expectancy and death from cardiomyopathy amongst carriers of Duchenne and Becker muscular dystrophy in Scotland.

OBJECTIVES: To assess life expectancy and cardiovascular mortality in carriers of Duchenne and Becker muscular dystrophy. DESIGN: Family pedigrees of individuals affected with these conditions, held by the four genetics centres in Scotland, were examined to identify a cohort of definite carriers. Electronic death registration data, held by the General Register Office for Scotland, were used to identify death certificates of carriers who had died, to obtain age at death and cause of death. Survival and mortality data were obtained for the general population for comparison. PATIENTS: 397 definite carriers in 202 pedigrees were identified from which 94 deaths were identified by record linkage to death certificates. MAIN OUTCOME MEASURES: Observed numbers surviving to certain ages and numbers dying of cardiac causes were compared with expected numbers calculated from general population data. RESULTS: There were no significant differences between observed and expected numbers surviving to ages 40-90. The standardised mortality ratio for the 371 carriers alive in 1974 was 0.53 (95% confidence interval 0.32 to 0.82). CONCLUSIONS: Whereas female carriers may have clinical features of cardiomyopathy, this study does not suggest that this is associated with reduced life expectancy or increased risk of cardiac death. Routine cardiac surveillance of obligate carriers is therefore probably unnecessary.

Unemployment and deprivation are associated with a poorer outcome following percutaneous coronary angioplasty.

This prospective observational study aimed to assess the impact of employment status and deprivation on quality of life 12 months after percutaneous coronary intervention (PCI). Patients completed a questionnaire at baseline and at 1 year follow-up including a health utility score (EQ-5D), symptoms and employment status. Deprivation was assessed using the Carstairs' deprivation category based on area postcodes. The majority (79.6%) of patients of working age returned to work within 12 months. Unemployment was associated with a lower quality of life (QoL) at baseline (0.49 (0.32) vs 0.61 (0.27), p=0.002) and less improvement in QoL 1 year after PCI (0.15 (0.37) vs 0.26 (0.31), p<0.012). Furthermore, unemployed patients had significantly less improvement in chest pain score (p=0.002) and breathlessness (p<0.001). Unemployed patients from the most deprived areas had lowest QoL at follow-up and least improvement in QoL at 1 year. Unemployment and deprivation are associated with poorer outcomes following PCI.

Effects of changing clinical practice on costs and outcomes of percutaneous coronary intervention between 1998 and 2002.

AIM: To assess the effect of changing clinical practice on the costs and outcomes of percutaneous coronary intervention (PCI) between 1998 and 2002. SETTING: Two tertiary interventional centres. PATIENTS: Consecutive patients undergoing PCI over a 12-month period between 1998 and 2002. DESIGN: Comparative observational study of costs and 12-month clinical outcomes of consecutive PCI procedures in 1998 (n = 1047) and 2002 (n = 1346). Clinical data were recorded in the Scottish PCI register. Repeat PCI, coronary artery bypass graft and mortality were obtained by record linkage. Costs of equipment were calculated using a computerised bar-code system and standard National Health Service reference costs. RESULTS: Between 1998 and 2002, the use of bare metal stents increased from 44% to 81%, and the use of glycoprotein IIB/IIIA inhibitors increased from 0% to 14% of cases. During this time, a significant reduction was observed in repeat target-vessel PCI (from 8.4% to 5.1%, p = 0.001), any repeat PCI (from 11.7% to 9.2%, p = 0.05) and any repeat revascularisation (from 15.1% to 11.3%, p = 0.009) within 12 months. Significantly higher cost per case in 2002 compared with 1998 (mean (standard deviation) 2311 pounds (1158) v 1785 pounds (907), p<0.001) was mainly due to increased contribution from bed-day costs in 2002 (45.0% (16.3%) v 26.2% (12.6%), p = 0.01) associated with non-elective cases spending significantly longer in hospital (6.22 (4.3) v 4.6 (4.3) days, p = 0.01). CONCLUSIONS: Greater use of stents and glycoprotein IIb/IIIa inhibitors between 1998 and 2002 has been accompanied by a marked reduction in the need for repeat revascularisation. Longer duration of hospital stay for non-elective cases is mainly responsible for increasing costs. Strategies to reduce the length of stay could considerably reduce the costs of PCI.

Urgent in-patient coronary angiography: a comparison of centres with and without cardiac catheter facilities.

OBJECTIVES: To review the referral of patients to a tertiary centre for urgent angiography and to determine if there are differences in invasive treatment strategies for patients with acute coronary syndrome (ACS). METHODS: There were 2 parts to the study, a retrospective part over 3.5 years from a computerised cardiac laboratory booking data base and a prospective part over 3 months. RESULTS: There were 1190 urgent in-patient angiograms performed with 499 (42%) admitted initially to the tertiary centre while the remaining 691 (58%) were admitted to district general hospitals (DGH), with no on-site access to a cardiac laboratory, and subsequently transferred to the tertiary centre. Once referred, DGH patients waited longer for their angiogram (2.7 +/- 3.2 vs 2.0 +/- 2.8 days, p < 0.0001). Interestingly, DGH patients appear to spend an average of 4 days in hospital prior to referral for angiography. DGH patients were more likely to have a higher Thrombosis in Myocardial Infarction (TIMI) risk score at presentation and following angiography were more likely to have coronary artery bypass graft (CABG) or percutaneous coronary intervention (PCI) and less likely to have angiographically normal arteries. CONCLUSIONS: Our findings are consistent with previous studies demonstrating that access to coronary angiography varies considerably between hospitals. However, we have demonstrated that patients in DGHs wait on average 4 days before referral for coronary angiography suggesting that there may be triage based on initial responses to medical therapy. Further research is needed to determine whether this has a direct effect on outcomes.

Influence of socioeconomic status on clinical outcomes and quality of life after percutaneous coronary intervention.

OBJECTIVES: To determine whether socioeconomic status (SES) influences clinical outcomes and quality of life after percutaneous coronary intervention (PCI). DESIGN: Prospective observational study. SETTING: Two interventional cardiac centres. PARTICIPANTS: 1346 consecutive patients undergoing PCI over a 12-month period. OUTCOMES: Self reported health-related quality of life (HRQoL; EuroQol-5 Dimensions (EQ-5D); EuroQol Visual Analogue Scale (EQ-VAS)), repeat angiography, revascularisation, hospital admission, myocardial infarction and death within 12 months, by SES derived using postal address code. MAIN RESULTS: No significant differences were found between patients with high and low SES in the occurrence of repeat angiography (p = 0.55), repeat revascularisation (PCI, p = 0.81, CAEG, p = 0.27), total cardiac hospitalisation (p = 0.10), myocardial infarction (p = 0.97) or death 12 months after PCI (p = 0.88). Non-procedure-related readmissions were higher in patients with low SES (18.6% v 13.7%; p = 0.025). After adjustment for confounding factors, patients with low SES had lower HRQoL scores at baseline (95% CI for difference 0.01 to 0.14; p = 0.003) and at 12 months (95% CI 0.07 to 0.17; p<0.001) compared with those with high SES. CONCLUSIONS: Clinical outcomes were similar for patients in different SES groups. Patients with low SES had considerably more non-procedure-related readmissions and lower quality-of-life scores. Future studies on HRQoL after coronary revascularisation should take account of these important differences related to SES.

Variations in clinical decision-making between cardiologists and cardiac surgeons; a case for management by multidisciplinary teams?

OBJECTIVE: To assess variations in decisions to revascularise patients with coronary heart disease between general cardiologists, interventional cardiologists and cardiac surgeons DESIGN: Six cases of coronary heart disease were presented at an open meeting in a standard format including clinical details which might influence the decision to revascularise. Clinicians (n = 53) were then asked to vote using an anonymous electronic system for one of 5 treatment options: medical, surgical (CABG), percutaneous coronary intervention (PCI) or initially medical proceeding to revascularisation if symptoms dictated. Each case was then discussed in an open forum following which clinicians were asked to revote. Differences in treatment preference were compared by chi squared test and agreement between groups and between voting rounds compared using Kappa. RESULTS: Surgeons were more likely to choose surgery as a form of treatment (p = 0.034) while interventional cardiologists were more likely to choose PCI (p = 0.056). There were no significant differences between non-interventional and interventional cardiologists (p = 0.13) in their choice of treatment. There was poor agreement between all clinicians in the first round of voting (Kappa 0.26) but this improved to a moderate level of agreement after open discussion for the second vote (Kappa 0.44). The level of agreement among surgeons (0.15) was less than that for cardiologists (0.34) in Round 1, but was similar in Round 2 (0.45 and 0.45 respectively). CONCLUSION: In this case series, there was poor agreement between cardiac clinical specialists in the choice of treatment offered to patients. Open discussion appeared to improve agreement. These results would support the need for decisions to revascularise to be made by a multidisciplinary panel.

Clinical features remain important for the diagnosis of infective endocarditis in the modern era.

BACKGROUND: Infective endocarditis (IE) can be difficult to diagnose, due to multiple (often non-specific) presenting features. AIM: To assess the predictive accuracy of classical clinical features and blood investigations readily available at the time of presentation. DESIGN: Cross-sectional analysis. METHODS: We studied 29 IE cases and 79 controls (clinically suspicious contemporaneous cases where IE was subsequently excluded) from a hospital-based group of patients referred to a cardiac department with possible infective endocarditis. Patients were identified from the echocardiography database. Cases were defined by final diagnosis. Symptoms, signs, risk factors for IE and blood investigations were recorded from case notes and examined by univariate and multivariate analyses. RESULTS: The sensitivity, specificity, and positive and negative predictive values of transthoracic echocardiography (TTE) for detection of IE in clinically suspected cases were 71%, 98%, 57% and 99%, respectively. Univariate analyses revealed a significant association between IE and several clinical features. Under multivariate analysis, previous heart valve surgery (OR 13.3, 90%CI 3.2-55.6), positive blood cultures (OR 17.2, 90%CI 4.9-58.8), signs of embolism (OR 11.4, 90%CI 3.0-43.5), a new, altered or changing murmur (OR 10.3, 90%CI 2.8-38.5) and splenomegaly (OR 18.2, 90%CI 3.6-90.9) were independent predictors for IE. DISCUSSION: Clinical features at presentation continue to be important for the diagnosis of IE. Features such as positive blood cultures, signs of embolism and a changing heart murmur should be used to guide investigation and treatment of IE prior to echocardiography, or when TTE is negative.

Direct comparison of selective endothelin A and non-selective endothelin A/B receptor blockade in chronic heart failure.

OBJECTIVE: To investigate the potential differential effects of selective endothelin (ET) A and dual ET-A/B receptor blockade in patients with chronic heart failure. METHODS: Nine patients with chronic heart failure (New York Heart Association class II-III) each received intravenous infusions of BQ-123 alone (selective ET-A blockade) and combined BQ-123 and BQ-788 (dual ET-A/B blockade) in a randomised, placebo controlled, three way crossover study. RESULTS: Selective ET-A blockade increased cardiac output (maximum mean (SEM) 33 (12)%, p < 0.001) and reduced mean arterial pressure (maximum -13 (4)%, p < 0.001) and systemic vascular resistance (maximum -26 (8)%, p < 0.001), without changing heart rate (p = 0.38). Dual ET-A/B blockade significantly reduced the changes in all these haemodynamic variables compared with selective ET-A blockade (p < 0.05). Selective ET-A blockade reduced pulmonary artery pressure (maximum 25 (7)%, p = 0.01) and pulmonary vascular resistance (maximum 72 (39)%, p < 0.001). However, there was no difference between these effects and those seen with dual ET-A/B blockade. Unlike selective ET-A blockade, dual ET-A/B blockade increased plasma ET-1 concentrations (by 47 (4)% with low dose and 61 (8)% with high dose, both p < 0.05). CONCLUSIONS: While there appeared to be similar reductions in pulmonary pressures with selective ET-A and dual ET-A/B blockade, selective ET-A blockade caused greater systemic vasodilatation and did not affect ET-1 clearance. In conclusion, there are significant haemodynamic differences between selective ET-A and dual ET-A/B blockade, which may determine responses in individual patients.

Management of chronic heart failure: perceived needs of general practitioners in light of the new general medical services contract.

BACKGROUND: Despite the existence of several chronic heart failure (CHF) guidelines the treatment of patients with CHF is suboptimal. The new general medical services (GMS) contract in primary care has only three specific performance indicators for patients with left ventricular dysfunction. The aim of this current questionnaire survey was to assess the views of general practitioners (GPs) on CHF treatments and services in light of the new GMS contract. METHODS AND RESULTS: All local GPs (717) were sent a questionnaire. Fifty three per cent were returned. Forty five per cent of GPs had access to a community CHF nurse. Having read a national guideline (SIGN) and having the support of a CHF nurse did not seem to affect the knowledge of GPs in terms of perceived benefits of drug treatments. GPs with access to a specialist CHF nurse service attached more importance to it than those with no specialist nurse (p = 0.003). CONCLUSIONS: Most GPs were aware of the existence of a national guideline but many had not read it. There was little or no difference in the knowledge level for various evidence based treatments between GPs who had or had not read the guideline suggesting that reading guidelines may not be a key factor in determining knowledge. Support for a specialist CHF nurse was higher among GPs who already had this service, suggesting that this service is valued. The new GMS contract may improve identification and diagnosis of patients with CHF but there is a danger that it may fall short of ensuring optimal treatment for patients with CHF.