Prevalence of atrial fibrillation in the general population and in high-risk groups: the ECHOES study.

AIMS: To establish the prevalence of atrial fibrillation (AF) in the general population in the UK, and in those with risk factors. METHODS AND RESULTS: The prevalence of AF on electrocardiography was established in prospectively selected groups: 3960 randomly selected from the population, aged 45+; 782 with a previous diagnosis of heart failure; and 1062 with a record of myocardial infarction, hypertension, angina, or diabetes. Patients were also assessed clinically and with echocardiography. Mortality was tracked for 8 years. Atrial fibrillation was found in 78 of the random population sample (2.0%). Prevalence was 1.6% in women and 2.4% in men, rising with age from 0.2% in those aged 45-54 to 8.0% in those aged 75 and older. Half of all cases were in patients aged 75 and older. Only 23 of the 78 (29.5%) of those in AF took warfarin. Of the 782 patients, 175 (22.4%) with a diagnosis of heart failure were in AF, with normal left ventricular function in 95 (54.3%) of these. Atrial fibrillation was found in 14 of the 244 (5.7%) of those with a history of myocardial infarction, 15 of the 388 (3.9%) of those with hypertension, 15 of the 321 (4.7%) of those with angina, and 11 of the 208 (5.3%) of diabetics. Adjusting for age and sex, mortality was 1.57 times higher for those in AF. CONCLUSION: Atrial fibrillation is common in the elderly and those with clinical risk factors. Screening these groups would identify many with AF. Use of anticoagulation was low at the time of the initial assessments in the late 1990s; practice may have changed recently.

The cost effectiveness of REACH-HF and home-based cardiac rehabilitation compared with the usual medical care for heart failure with reduced ejection fraction: A decision model-based analysis.

BACKGROUND: The REACH-HF (Rehabilitation EnAblement in CHronic Heart Failure) trial found that the REACH-HF home-based cardiac rehabilitation intervention resulted in a clinically meaningful improvement in disease-specific health-related quality of life in patients with reduced ejection fraction heart failure (HFrEF). The aims of this study were to assess the long-term cost-effectiveness of the addition of REACH-HF intervention or home-based cardiac rehabilitation to usual care compared with usual care alone in patients with HFrEF. DESIGN AND METHODS: A Markov model was developed using a patient lifetime horizon and integrating evidence from the REACH-HF trial, a systematic review/meta-analysis of randomised trials, estimates of mortality and hospital admission and UK costs at 2015/2016 prices. Taking a UK National Health and Personal Social Services perspective we report the incremental cost per quality-adjusted life-year (QALY) gained, assessing uncertainty using probabilistic and deterministic sensitivity analyses. RESULTS: In base case analysis, the REACH-HF intervention was associated with per patient mean QALY gain of 0.23 and an increased mean cost of £400 compared with usual care, resulting in a cost per QALY gained of £1720. Probabilistic sensitivity analysis indicated a 78% probability that REACH-HF is cost effective versus usual care at a threshold of £20,000 per QALY gained. Results were similar for home-based cardiac rehabilitation versus usual care. Sensitivity analyses indicate the findings to be robust to changes in model assumptions and parameters. CONCLUSIONS: Our cost-utility analyses indicate that the addition of the REACH-HF intervention and home-based cardiac rehabilitation programmes are likely to be cost-effective treatment options versus usual care alone in patients with HFrEF.

The effects and costs of home-based rehabilitation for heart failure with reduced ejection fraction: The REACH-HF multicentre randomized controlled trial.

BACKGROUND: Cardiac rehabilitation improves health-related quality of life (HRQoL) and reduces hospitalizations in patients with heart failure, but international uptake of cardiac rehabilitation for heart failure remains low. DESIGN AND METHODS: The aim of this multicentre randomized trial was to compare the REACH-HF (Rehabilitation EnAblement in CHronicHeart Failure) intervention, a facilitated self-care and home-based cardiac rehabilitation programme to usual care for adults with heart failure with reduced ejection fraction (HFrEF). The study primary hypothesis was that the addition of the REACH-HF intervention to usual care would improve disease-specific HRQoL (Minnesota Living with Heart Failure questionnaire (MLHFQ)) at 12 months compared with usual care alone. RESULTS: The study recruited 216 participants, predominantly men (78%), with an average age of 70 years and mean left ventricular ejection fraction of 34%. Overall, 185 (86%) participants provided data for the primary outcome. At 12 months, there was a significant and clinically meaningful between-group difference in the MLHFQ score of -5.7 points (95% confidence interval -10.6 to -0.7) in favour of the REACH-HF intervention group ( p = 0.025). With the exception of patient self-care ( p < 0.001) there was no significant difference in other secondary outcomes, including clinical events ( p > 0.05) at follow-up compared with usual care. The mean cost of the REACH-HF intervention was £418 per participant. CONCLUSIONS: The novel REACH-HF home-based facilitated intervention for HFrEF was clinically superior in disease-specific HRQoL at 12 months and offers an affordable alternative to traditional centre-based programmes to address current low cardiac rehabilitation uptake rates for heart failure.

A randomised controlled trial of a facilitated home-based rehabilitation intervention in patients with heart failure with preserved ejection fraction and their caregivers: the REACH-HFpEF Pilot Study.

INTRODUCTION: Home-based cardiac rehabilitation may overcome suboptimal rates of participation. The overarching aim of this study was to assess the feasibility and acceptability of the novel Rehabilitation EnAblement in CHronic Hear Failure (REACH-HF) rehabilitation intervention for patients with heart failure with preserved ejection fraction (HFpEF) and their caregivers. METHODS AND RESULTS: Patients were randomised 1:1 to REACH-HF intervention plus usual care (intervention group) or usual care alone (control group). REACH-HF is a home-based comprehensive self-management rehabilitation programme that comprises patient and carer manuals with supplementary tools, delivered by trained healthcare facilitators over a 12 week period. Patient outcomes were collected by blinded assessors at baseline, 3 months and 6 months postrandomisation and included health-related quality of life (primary) and psychological well-being, exercise capacity, physical activity and HF-related hospitalisation (secondary). Outcomes were also collected in caregivers.We enrolled 50 symptomatic patients with HF from Tayside, Scotland with a left ventricular ejection fraction ≥45% (mean age 73.9 years, 54% female, 100% white British) and 21 caregivers. Study retention (90%) and intervention uptake (92%) were excellent. At 6 months, data from 45 patients showed a potential direction of effect in favour of the intervention group, including the primary outcome of Minnesota Living with Heart Failure Questionnaire total score (between-group mean difference -11.5, 95% CI -22.8 to 0.3). A total of 11 (4 intervention, 7 control) patients experienced a hospital admission over the 6 months of follow-up with 4 (control patients) of these admissions being HF-related. Improvements were seen in a number intervention caregivers' mental health and burden compared with control. CONCLUSIONS: Our findings support the feasibility and rationale for delivering the REACH-HF facilitated home-based rehabilitation intervention for patients with HFpEF and their caregivers and progression to a full multicentre randomised clinical trial to test its clinical effectiveness and cost-effectiveness. TRIAL REGISTRATION NUMBER: ISRCTN78539530.

Evaluation of B-type natriuretic peptide for validation of a heart failure register in primary care.

BACKGROUND: Diagnosing heart failure and left ventricular systolic dysfunction is difficult on clinical grounds alone. We sought to determine the accuracy of a heart failure register in a single primary care practice, and to examine the usefulness of b-type (or brain) natriuretic peptide (BNP) assay for this purpose. METHODS: A register validation audit in a single general practice in the UK was carried out. Of 217 patients on the heart failure register, 56 of 61 patients who had not been previously investigated underwent 12-lead electrocardiography and echocardiography within the practice site. Plasma was obtained for BNP assay from 45 subjects, and its performance in identifying echocardiographic abnormalities consistent with heart failure was assessed by analysing area under receiver operator characteristic (ROC) curves. RESULTS: 30/217 were found to have no evidence to suggest heart failure on notes review and were probably incorrectly coded. 70/112 who were previously investigated were confirmed to have heart failure. Of those not previously investigated, 24/56 (42.9%) who attended for the study had echocardiographic left ventricular systolic dysfunction. A further 8 (14.3%) had normal systolic function, but had left ventricular hypertrophy or significant valve disease. Overall, echocardiographic features consistent with heart failure were found in only 102/203 (50.2%). BNP was poor at discriminating those with and without systolic dysfunction (area under ROC curve 0.612), and those with and without any significant echocardiographic abnormality (area under ROC curve 0.723). CONCLUSION: In this practice, half of the registered patients did not have significant cardiac dysfunction. On-site echocardiography identifies patients who can be removed from the heart failure register. The use of BNP assay to determine which patients require echocardiography is not supported by these data.

Home-based exercise rehabilitation in addition to specialist heart failure nurse care: design, rationale and recruitment to the Birmingham Rehabilitation Uptake Maximisation study for patients with congestive heart failure (BRUM-CHF): a randomised controlled trial.

BACKGROUND: Exercise has been shown to be beneficial for selected patients with heart failure, but questions remain over its effectiveness, cost-effectiveness and uptake in a real world setting. This paper describes the design, rationale and recruitment for a randomised controlled trial that will explore the effectiveness and uptake of a predominantly home-based exercise rehabilitation programme, as well as its cost-effectiveness and patient acceptability. METHODS/DESIGN: Randomised controlled trial comparing specialist heart failure nurse care plus a nurse-led predominantly home-based exercise intervention against specialist heart failure nurse care alone in a multiethnic city population, served by two NHS Trusts and one primary care setting, in the United Kingdom.169 English speaking patients with stable heart failure, defined as systolic impairment (ejection fraction < or = 40%). with one or more hospital admissions with clinical heart failure or New York Heart Association (NYHA) II/III within previous 24-months were recruited.Main outcome measures at 1 year: Minnesota Living with Heart Failure Questionnaire, incremental shuttle walk test, death or admission with heart failure or myocardial infarction, health care utilisation and costs. Interviews with purposive samples of patients to gain qualitative information about acceptability and adherence to exercise, views about their treatment, self-management of their heart failure and reasons why some patients declined to participate. The records of 1639 patients managed by specialist heart failure services were screened, of which 997 (61%) were ineligible, due to ejection fraction>40%, current NYHA IV, no admission or NYHA II or more within the previous 2 years, or serious co-morbidities preventing physical activity. 642 patients were contacted: 289 (45%) declined to participate, 183 (39%) had an exclusion criterion and 169 (26%) agreed to randomisation. DISCUSSION: Due to safety considerations for home-exercise less than half of patients treated by specialist heart failure services were eligible for the study. Many patients had co-morbidities preventing exercise and others had concerns about undertaking an exercise programme.

Rheumatoid disease and ischaemic heart disease: insights from pathophysiology and vascular biology.

Rheumatoid disease (RD) is a multisystem inflammatory disorder, which is associated with an increased cardiovascular mortality, thought to be due to ischaemic heart disease (IHD). The precise mechanisms causing increased IHD in RD are unclear. However, there is increasing recognition that atherosclerosis is another chronic inflammatory condition, which shares several pathophysiological features with RD. For example, endothelial damage/dysfunction, platelet activation, hypercoagulability and angiogenesis are well-recognised in both disease processes. Furthermore, RD may influence traditional risk factors such as dyslipidaemia. Although the exact reasons for the increased ischaemic burden are unclear, physicians should place a high priority upon reducing cardiovascular risk in sufferers of RD. This review summarises factors that might contribute to the pathogenesis of IHD in RD. Discussion will focus upon features shared by atherosclerotic and rheumatoid processes, as well as possible interactions between RD and conventional IHD risk factors.

Drug development and the importance of ethnicity: lessons from heart failure management and implications for hypertension.

Heart failure is a common condition, associated with both poor prognosis and poor quality of life. In contrast to all other cardiovascular diseases, the prevalence of heart failure is increasing in the western world, and is likely to continue to do so as the population ages. In the UK, a significant proportion of patients with heart failure come from South Asian and African Caribbean ethnic groups. A large body of evidence exists that there may be epidemiological and pathophysiological differences between patients with heart failure from different ethnic groups. Treatments such as ACE inhibitors, which are now part of standard heart failure therapy, have an evidence base consisting of trials in patients of almost exclusively white ethnicity. Such treatments may not be equally effective in patients from other ethnic groups. This review will discuss the current evidence for heart failure management with respect to ethnicity, and consider the implications for future drug development and implications for antihypertensive therapy.

Heart failure--the importance of ethnicity.

Heart failure is a major public health problem in the Western world. Aetiological factors involved in its development include hypertension, diabetes, and ischaemic heart disease--all of which differ in prevalence, and possibly mechanism, between patients of differing ethnicity. Unfortunately, epidemiological and therapeutic trials have involved almost exclusively white populations, and evidence from these trials cannot necessarily be assumed to be generalisable to populations that include high proportions of patients from other ethnic origins. This review will discuss the mechanistic and therapeutic differences that exist in heart failure between those of European origin, and patients from the major ethnic minority groups of the UK.

An 8-year follow-up study of acute admissions with heart failure in a multiethnic population.

In 1994, we reported a cross-sectional survey of acute heart failure admissions to a city centre hospital serving a multiethnic population and found ethnic differences in aetiological factors and short-term (in-patient) mortality. We analysed long-term mortality data for this original survey cohort after 8 years' follow-up. At 8 years' follow-up, the total mortality was 90.5% amongst Europeans and 87.0% amongst non-Europeans (log rank test, P=0.0705). The non-European patients had significantly better survival at all time points until 6 years, after which the survival curves start to converge. In univariate analysis, age <75.6 years (that is, the median age of the whole cohort), use of beta-blockers, use of ACE inhibitors, and absence of atrial fibrillation were significantly associated with increased survival. In addition, patients who had had an echocardiographic examination had significantly prolonged survival when compared to those who did not. Using a Cox multiple regression analysis, age, renal impairment, atrial fibrillation, absence of echocardiography, absence of beta-blockers or ACE inhibitor use (and not ethnicity) remained significant predictors of mortality at 8 years. While this follow-up study has suggested that survival following admission for acutely decompensated heart failure is not different between different ethnic groups when corrected for age, it is clear from the younger age of heart failure patients from ethnic minority groups and the relatively high prevalence, that the burden of heart failure is greater in these populations. Future observational and therapeutic trials in heart failure should include sufficient numbers of participants from ethnic minority groups to ensure that the results can be applied to the population at risk.

Observational longitudinal cohort study to determine progression to heart failure in a screened community population: the Echocardiographic Heart of England Screening Extension (ECHOES-X) study.

OBJECTIVES: Rescreen a large community cohort to examine the progression to heart failure over time and the role of natriuretic peptide testing in screening. DESIGN: Observational longitudinal cohort study. SETTING: 16 socioeconomically diverse practices in central England. PARTICIPANTS: Participants from the original Echocardiographic Heart of England Screening (ECHOES) study were invited to attend for rescreening. OUTCOME MEASURES: Prevalence of heart failure at rescreening overall and for each original ECHOES subgroup. Test performance of N Terminal pro-B-type Natriuretic Peptide (NT-proBNP) levels at different thresholds for screening. RESULTS: 1618 of 3408 participants underwent screening which represented 47% of survivors and 26% of the original ECHOES cohort. A total of 176 (11%, 95% CI 9.4% to 12.5%) participants were classified as having heart failure at rescreening; 103 had heart failure with reduced ejection fraction (HFREF) and 73 had heart failure with preserved ejection fraction (HFPEF). Sixty-eight out of 1232 (5.5%, 95% CI 4.3% to 6.9%) participants who were recruited from the general population over the age of 45 and did not have heart failure in the original study, had heart failure on rescreening. An NT-proBNP cut-off of 400 pg/mL had sensitivity for a diagnosis of heart failure of 79.5% (95% CI 72.4% to 85.5%) and specificity of 87% (95% CI 85.1% to 88.8%). CONCLUSIONS: Rescreening identified new cases of HFREF and HFPEF. Progression to heart failure poses a significant threat over time. The natriuretic peptide cut-off level for ruling out heart failure must be low enough to ensure cases are not missed at screening.

Subclinical thyroid dysfunction and cardiac function amongst minority ethnic groups in the UK: a cross sectional study.

BACKGROUND: Subclinical thyroid disease is associated with abnormal cardiovascular haemodynamics and increased risk of heart failure. The burden of raised/low thyroid stimulating hormone (TSH) levels amongst South Asian (SA) and African-Caribbean (AC) minority groups in the UK is not well defined. Given that these groups are particularly susceptible to CVD, we hypothesised that STD would reflect abnormal cardiac function and heightened cardiovascular risk in these ethnic groups. METHODS: We examined SA (n=1111, 56% male, mean age 57.6 yrs) and AC (n=763, 44% male, mean age 59.2 yrs) participants from a large heart failure screening study. Euthyroidism is defined as TSH (0.4 - 4.9 mlU/l), subclinical hypothyroidism is defined as a raised TSH with normal serum free thyroxine (FT4) concentrations (9-19 pmol/l). Subclinical hyperthyroidism is defined as a low TSH with both FT4 and free triiodothyronine (FT3) concentrations within range (2.6-5.7 pmol/l). RESULTS: Across ethnic groups, prevalence of subclinical hypothyroidism was 2.9% (95% CI 2.1-3.7), and of hyperthyroidism was 2.0% (1.4-2.7). Hyperthyroidism was more common amongst SA compared to AC (2.8% vs. 0.9%, P=0.017), while rates of subclinical hypothyroidism were similar. On multivariate analysis of variations in subclinical thyroid function, ethnicity was not independently significant. CONCLUSION: The prevalence of subclinical thyroid disorders amongst SA and AC minority groups in Britain reflects levels reported in other populations. The clinical cardiovascular significance of subclinical thyroid disease is unclear, and it does not appear to be ethnically specific.

Plasma indices of angiogenesis in rheumatoid disease: relationship to cardiovascular risk factors and cardiac function.

INTRODUCTION: Rheumatoid Disease (RD) is associated with increased rates of cardiovascular disease (CVD). Angiogenesis is central to RD, and well-recognized in CVD. We hypothesised that plasma levels of two indices associated with angiogenesis, vascular endothelial growth factor (VEGF) and angiogenin, would be higher among RD patients compared to healthy controls (HC), would relate to CVD risk factors, calculated 10-year coronary heart disease (CHD) and stroke risk scores. METHODS: 144 clinic patients with established RD and 63 HC were recruited in a cross-sectional study. RD patients were grouped according to the presence (RD-CVD, n=73 or absence (non-CVD RD; n=71) of CVD risk factors. Angiogenin and VEGF levels were quantified by ELISA. RESULTS: There were no significant differences for VEGF or angiogenin, between RD-CVD, non-CVD RD and HC groups (p=NS). Calculated risks for both CHD (p=0.017) and stroke (p=0.016) were higher when RD-CVD was compared to non-CVD RD and HC. Upon multivariate analysis, methotrexate use (p=0.006) and prior mycocardial infarction (MI) (p=0.034) were associated with higher angiogenin levels; body mass index (BMI) (p=0.034) and presence of RD (p=0.029) itself predicted lower levels. For RD patients, serum creatinine (p<0.001) and CRP levels, VEGF levels, and NSAID/COX2 inhibitor use (all p<0.05) were independently associated with CHD risk; plasma VEGF and serum creatinine levels were independently associated with stroke risk (p<0.05). CONCLUSIONS: Although levels of angiogenin were not significantly different between HC and RD patients, RD may have some influence on their variation. Methotrexate use and prior MI predicted higher angiogenin levels, whilst levels of VEGF were negatively associated with 10-year CHD and stroke risk.

Antithrombotic therapy for heart failure in sinus rhythm.

Although the risk of thromboembolism in chronic heart failure is high even in the absence of atrial fibrillation, the risk to benefit ratio of anticoagulation vs. antiplatelet therapy or no antithrombotic therapy is poorly defined in this population. Post hoc analysis of large therapeutic heart failure trials has estimated the risk of thromboembolism to be between 1 and 4.5%. However, most of these studies have included some patients with atrial fibrillation, and thromboembolism was not a predefined endpoint. At present, the evidence for either anticoagulation or antiplatelet therapy is limited and the results from current large-scale randomized studies are awaited. From the randomized studies carried out thus far, there is a beneficial trend in favour of anticoagulation therapy, with less hospitalization for heart failure compared with patients taking aspirin.

Plasma indices of endothelial and platelet activation in Rheumatoid Disease: relationship to cardiovascular co-morbidity.

BACKGROUND: Rheumatoid Disease (RD) is associated with ischaemic heart disease (IHD). We sought to investigate whether abnormalities of endothelial function and platelet activation in patients with established RD were related to co-morbid cardiovascular risk factors. METHODS: In a cross-sectional study, RD patients with no cardiac risk factors and normal cardiac function (RD, n=73), those with cardiovascular disease or risk factors and normal cardiac function (RD-risk, n=59), and those with left ventricular systolic dysfunction (RD-LVSD, n=21) were recruited, and compared to healthy controls (HC, n=76). Plasma levels of von Willebrand factor (vWF, an index of endothelial damage/dysfunction), soluble E-selectin (sE-sel, a marker of endothelial activation), and soluble P-selectin (sP-sel, an index of platelet activation) were studied. RESULTS: Plasma levels of vWF and sP-sel (but not sE-sel) were significantly higher among 153 RD patients compared to controls (p=0.002 and p<0.001, respectively). Levels of vWF progressively rose with increasing cardiovascular risk across the four subgroups (p for trend<0.001). Previous IHD was independently associated with vWF levels, and diabetes mellitus (DM) was similarly associated with all three markers. RD itself and beta-blocker use were associated with sP-sel. CONCLUSION: Plasma levels of vWF and sP-sel are higher among RD patients. Levels of vWF were particularly influenced by cardiac risk factor status, and associated with known IHD and DM.

Elevated angiogenin levels in chronic heart failure.

BACKGROUND: Abnormal indices of angiogenesis have been reported in chronic heart failure (CHF). We tested the hypothesis that circulating angiogenin (a potent inducer of neovascularization in vivo) is higher in CHF patients compared with controls and associated with indices of CHF severity: brain natriuretic peptide (BNP), Simpson's left ventricular ejection fraction (EF), and New York Heart Association (NYHA) class. METHODS: Using a cross-sectional approach, we measured serum angiogenin and BNP levels in 109 consecutive patients with CHF (85 males; mean age 60 (standard deviation (SD) 10 yrs) and 112 asymptomatic controls with normal cardiac function and related levels to echocardiographic parameters. RESULTS: Angiogenin was significantly higher in CHF patients compared to controls (P < 0.001). On univariate analysis, angiogenin was positively associated with age, plasma glucose, insulin, and BNP (all P < 0.001); and negatively correlated with diastolic blood pressure (P = 0.04) and EF (P = 0.002). Angiogenin levels increased in an ordinal fashion with NYHA class, exaggerated by the presence of diabetes mellitus (pseudo R2 = 0.15, P < 0.001). In multivariate analysis, angiogenin levels were only associated with deteriorating NYHA classification (beta = 0.14 (95% confidence interval (CI) 0.09-0.19), P < 0.001). Angiogenin was also a modest discriminator for the presence of CHF (area under the curve 0.72; 95% CI 0.62-0.82), P < 0.001). CONCLUSION: Angiogenin is related to worsening heart failure severity (NYHA classification), with the highest levels in NYHA class III. Further research is warranted to determine the validity of angiogenin in a diagnostic and prognostic capacity in CHF.

Effects of white European, African Caribbean and South Asian ethnicity on homocysteine levels in patients with systolic heart failure.

BACKGROUND: Patients with heart failure of any cause have elevated homocysteine compared to healthy controls. A number of studies in the UK and other western countries have documented higher levels of homocysteine among South Asian than among White European or African Caribbean subjects both in health and in disease, and have suggested that dietary deficiency of folate is the main cause for the difference. METHODS: Plasma homocysteine, vitamin B(12), and folate levels were measured in a multiethnic UK heart failure clinic population (n=112), and compared to matched control subjects (n=131). RESULTS: Plasma homocysteine levels were significantly higher in heart failure patients than controls (p<0.001), a result that was consistent across all ethnic groups. There was no difference in homocysteine levels by ethnic group in either patients (p=0.898) or controls (p=0.368). There was no significant difference in levels of folate or B(12) among patients or controls. Using a stepwise linear regression model, homocysteine levels in patients and controls were independently associated with age (p<0.001), vitamin B(12) (p<0.001), folate (p<0.001) and healthy control status (p<0.001), but not with gender, ethnicity, diabetes status, smoking status or BNP levels. CONCLUSION: This study does not provide evidence of ethnic differences in homocysteine levels between White European, South Asian, and African Caribbean subjects with systolic heart failure. The lack of difference in levels of folate or B(12) among patients or controls, suggests that homocysteine levels - and differences previously seen between South Asians and other ethnic groups - may be driven by dietary factors.