Angiogenesis in ischaemic and hypertrophic hearts induced by long-term bradycardia.

Angiogenesis and improved left ventricular function as a consequence of long-term bradycardia were first demonstrated in normal hearts, either electrically paced (rabbits, pigs) or treated with a selective sinus blocking drug alinidine (rats). Here we review the evidence that chronic heart rate reduction can have similar effects in the heart with compromised vascular supply, due to either hypertensive or haemodynamic overload hypertrophy (rats, rabbits) or ischaemic damage (rats, rabbits, pigs). Bradycardia induced over several weeks increased capillarity in all hypertrophied hearts, and in border and remote left ventricular myocardium of infarcted hearts. In some, but not all cases, coronary blood flow was improved by heart rate reduction, suggesting enlargement of the resistance vasculature in some circumstances. Cardiac or left ventricular function indices, which were depressed by hypertrophy or ischaemic damage, were preserved or even enhanced by chronic heart rate reduction. The expansion of the capillary bed in the vascularly compromised heart induced by bradycardia may be stimulated by mechanical stretch of the endothelium and/or VEGF activated by chamber dilation and myocyte stretch. The increased number of capillaries and more homogeneous distribution of capillary perfusion would support the better pump function, even in the absence of higher coronary flow. The beneficial impact of chronic heart rate reduction on myocardial angiogenesis and function in cardiac hypertrophy and infarction may be major factor in the success of beta-blockers in treatment of human heart failure.

Management of acute coronary syndromes, a questionnaire survey of the clinical practice of cardiologists and other medical physicians belonging to west midland hospitals.

OBJECTIVE: To assess the management of acute coronary syndromes by cardiologists and other medical physicians in a clinical setting. DESIGN: Questionnaire survey consisting of 10 hypothetical clinical scenarios and four possible therapeutic options for each scenario. SETTING: Consultants and specialist registrars in Cardiology (with or without access to interventional facilities) and consultant physicians belonging to various hospitals in the west midland region of United Kingdom. MAIN OUTCOME MEASURES: Respondents' ability to recognise high risk patients and their management of the hypothetical clinical cases. To establish any differences in management strategy between cardiologists and general physicians, and whether these differences, if any, relate to access to interventional cardiac facilities. RESULTS: Overall no significant differences were found in the responses between cardiologists and general physicians with or without access to cardiac interventional facilities. However, cardiologists were more inclined to use percutaneous transluminal coronary angioplasty (PTCA) compared to other physicians (scenario 8, 18.4% vs. 6.7%, p = 0.05 and scenario 9, 44.9% vs. 26.7%, p = 0.01). In two other situations, physicians from institutions with access to interventional facilities were more inclined to use 'other' treatment strategies (intravenous nitrates, antiplatelet treatment, inotropes, Intra-aortic balloon pump) compared to their colleagues from non-tertiary hospitals with no interventional facility on site (scenario 3, 21.7% vs. 2.4%, p = 0.04) and more use of PTCA ( scenario 6, 52.2% vs. 26.8%, p = 0.04). CONCLUSIONS: The management of acute coronary syndromes in this questionnaire survey was satisfactory and evidence based. No real differences were found between the management strategies adopted by cardiologists or non-cardiologists. Physicians working in centres with interventional facilities were no more inclined towards using primary PTCA or rescue angioplasty than those working in centres without such facilities.

Ethnic differences in patient perceptions of heart failure and treatment: the West Birmingham heart failure project.

OBJECTIVE: To investigate further the hypothesis that ethnic groups would have different levels of knowledge and perceptions of congestive heart failure (CHF) and treatments for this condition, a cross sectional survey was conducted of patients who were attending the heart failure clinics in two teaching hospitals of Birmingham, UK, that serve a multiethnic population. METHODS: 103 patients with CHF (66 men, 37 women) were surveyed by standard questionnaire: 42 were white, 34 Indo-Asian, 22 Afro-Caribbean, and 5 Oriental. RESULTS: When asked about their beliefs about control of one's health, 22 (64.7%) of Indo-Asians felt that God/fate controlled their health. The majority of white patients tended to believe that the greatest factor influencing their health was the doctor (15 (35.7%)). Of the total study cohort, only 68 (66%) of patients were aware of their primary diagnosis of heart failure; the majority of Indo-Asians (21 (61.8%)) were not aware of their diagnosis. Half of Indo-Asians (17 (50%)) felt that heart failure was not severe, in contrast to 40.9% (n = 9) of Afro-Caribbeans and only 19.1% (n = 8) of white patients. Of the study cohort, 38 (36.9%) were taking their drugs because their doctor told them to, a response most common among the Indo-Asians. The majority of Indo-Asians (22 (64.7%)) and Afro-Caribbeans (14 (63.6%)) stated that they did not have, or did not know whether they had enough, information about their drug. The corresponding figure for white patients was 21.4% (n = 9). When asked whether they took their medication regularly as prescribed, 7 (31.8%) of Afro-Caribbeans reported that they did not take their drugs regularly. CONCLUSIONS: Our study has highlighted deficiencies in the knowledge of CHF among patients from ethnic minority groups, as well as deficiencies in the information being given to these patients. There is a clear need to invest more in patient education for CHF, with special emphasis on certain high risk subgroups.

Reliability of N-terminal proBNP assay in diagnosis of left ventricular systolic dysfunction within representative and high risk populations.

OBJECTIVE: To determine the performance of a new NT-proBNP assay in comparison with brain natriuretic peptide (BNP) in identifying left ventricular systolic dysfunction (LVSD) in randomly selected community populations. METHODS: Blood samples were taken prospectively in the community from 591 randomly sampled individuals over the age of 45 years, stratified for age and socioeconomic status and divided into four cohorts (general population; clinically diagnosed heart failure; patients on diuretics; and patients deemed at high risk of heart failure). Definite heart failure (left ventricular ejection fraction (LVEF) < 40%) was identified in 33 people. Samples were handled as though in routine clinical practice. The laboratories undertaking the assays were blinded. RESULTS: Using NT-proBNP to diagnose LVEF < 40% in the general population, a level of > 40 pmol/l had 80% sensitivity, 73% specificity, 5% positive predictive value (PPV), 100% negative predictive value (NPV), and an area under the receiver-operator characteristic curve (AUC) of 76% (95% confidence interval (CI) 46% to 100%). For BNP to diagnose LVSD, a cut off level of > 33 pmol/l had 80% sensitivity, 88% specificity, 10% PPV, 100% NPV, and AUC of 88% (95% CI 75% to 100%). Similar NPVs were found for patients randomly screened from the three other populations. CONCLUSIONS: Both NT-proBNP and BNP have value in diagnosing LVSD in a community setting, with similar sensitivities and specificities. Using a high cut off for positivity will confirm the diagnosis of LVSD but will miss cases. At lower cut off values, positive results will require cardiac imaging to confirm LVSD.

Management of chronic heart failure in the community: role of a hospital based open access heart failure service.

OBJECTIVE: To evaluate the role of an open access heart failure service based at a teaching hospital for the diagnosis and treatment optimisation of patients with heart failure in the community and to identify measures that may further enhance the effectiveness of such a service. SUBJECTS: 963 patients with suspected heart failure seen over an eight year period referred by their general practitioners to the cardiology department at a district general hospital. MAIN OUTCOME MEASURES: Presence or absence of left ventricular systolic dysfunction (LVSD) (left ventricular ejection fraction < 50% on echocardiography), and determination of the risk factors and predictors of LVSD. RESULTS: The majority of the patients were women (60% v 40%) and elderly (mean age 68.8 years). On echocardiography, only 30.8% were found to have LVSD. Patients were more likely to have LVSD if they were men (42.3% v 23.1%, p < 0.001, relative risk (RR) 1.8), were > 60 years of age (33.5% v 20.8%, p < 0.001, RR 1.6), or had a history of diabetes (49.4% v 29.1%, p < 0.001, RR 1.7), ischaemic heart disease (36.5% v 29.1%, p = 0.04, RR 1.3), or atrial fibrillation (52.6% v 27.8%, p < 0.001, RR 1.9). An abnormal ECG (48.4% v 19.5%, p < 0.001, RR 2.5) and cardiothoracic ratio > 0.5 on chest radiograph (44.3% v 17.8%, p < 0.001, RR 2.5) were found to be good predictors of LVSD. A normal ECG (negative predictive value 80.5%) and a cardiothoracic ratio of < 0.5 (negative predictive value 82.2%) can be used as baseline measures to identify patients with lower risk of developing LVSD (combined negative predictive value 87.9%). CONCLUSIONS: An open access heart failure clinic is effective for the diagnosis and management of chronic heart failure in community based patients. The presence of risk factors and simple baseline tests can be used to identify patients with LVSD in the community. The introduction of a protocol based on these findings into a referral system can improve the efficiency and cost effectiveness of such a service.

Systematic review and modelling of the investigation of acute and chronic chest pain presenting in primary care.

OBJECTIVES: To ascertain the value of a range of methods - including clinical features, resting and exercise electrocardiography, and rapid access chest pain clinics (RACPCs) - used in the diagnosis and early management of acute coronary syndrome (ACS), suspected acute myocardial infarction (MI), and exertional angina. DATA SOURCES: MEDLINE, EMBASE, CINAHL, the Cochrane Library and electronic abstracts of recent cardiological conferences. REVIEW METHODS: Searches identified studies that considered patients with acute chest pain with data on the diagnostic value of clinical features or an electrocardiogram (ECG); patients with chronic chest pain with data on the diagnostic value of resting or exercise ECG or the effect of a RACPC. Likelihood ratios (LRs) were calculated for each study, and pooled LRs were generated with 95% confidence intervals. A Monte Carlo simulation was performed evaluating different assessment strategies for suspected ACS, and a discrete event simulation evaluated models for the assessment of suspected exertional angina. RESULTS: For acute chest pain, no clinical features in isolation were useful in ruling in or excluding an ACS, although the most helpful clinical features were pleuritic pain (LR+ 0.19) and pain on palpation (LR+ 0.23). ST elevation was the most effective ECG feature for determining MI (with LR+ 13.1) and a completely normal ECG was reasonably useful at ruling this out (LR+ 0.14). Results from 'black box' studies of clinical interpretation of ECGs found very high specificity, but low sensitivity. In the simulation exercise of management strategies for suspected ACS, the point of care testing with troponins was cost-effective. Pre-hospital thrombolysis on the basis of ambulance telemetry was more effective but more costly than if performed in hospital. In cases of chronic chest pain, resting ECG features were not found to be very useful (presence of Q-waves had LR+ 2.56). For an exercise ECG, ST depression performed only moderately well (LR+ 2.79 for a 1 mm cutoff), although this did improve for a 2 mm cutoff (LR+ 3.85). Other methods of interpreting the exercise ECG did not result in dramatic improvements in these results. Weak evidence was found to suggest that RACPCs may be associated with reduced admission to hospital of patients with non-cardiac pain, better recognition of ACS, earlier specialist assessment of exertional angina and earlier diagnosis of non-cardiac chest pain. In a simulation exercise of models of care for investigation of suspected exertional angina, RACPCs were predicted to result in earlier diagnosis of both confirmed coronary heart disease (CHD) and non-cardiac chest pain than models of care based around open access exercise tests or routine cardiology outpatients, but they were more expensive. The benefits of RACPCs disappeared if waiting times for further investigation (e.g. angiography) were long (6 months). CONCLUSIONS: Where an ACS is suspected, emergency referral is justified. ECG interpretation in acute chest pain can be highly specific for diagnosing MI. Point of care testing with troponins is cost-effective in the triaging of patients with suspected ACS. Resting ECG and exercise ECG are of only limited value in the diagnosis of CHD. The potential advantages of RACPCs are lost if there are long waiting times for further investigation. Recommendations for further research include the following: determining the most appropriate model of care to ensure accurate triaging of patients with suspected ACS; establishing the cost-effectiveness of pre-hospital thrombolysis in rural areas; determining the relative cost-effectiveness of rapid access chest pain clinics compared with other innovative models of care; investigating how rapid access chest pain clinics should be managed; and establishing the long-term outcome of patients discharged from RACPCs.

Prevalence of left ventricular systolic dysfunction and heart failure in high risk patients: community based epidemiological study.

OBJECTIVES: To determine the prevalence of left ventricular systolic dysfunction, and of heart failure due to different causes, in patients with risk factors for these conditions. DESIGN: Epidemiological study, including detailed clinical assessment, electrocardiography, and echocardiography. SETTING: 16 English general practices, representative for socioeconomic status and practice type. PARTICIPANTS: 1062 patients (66% response rate) with previous myocardial infarction, angina, hypertension, or diabetes. MAIN OUTCOME MEASURES: Prevalence of systolic dysfunction, both with and without symptoms, and of heart failure, in groups of patients with each of the risk factors. RESULTS: Definite systolic dysfunction (ejection fraction <40%) was found in 54/244 (22.1%, 95% confidence interval 17.1% to 27.9%) patients with previous myocardial infarction, 26/321 (8.1%, 5.4% to 11.6%) with angina, 7/388 (1.8%, 0.7% to 3.7%) with hypertension, and 12/208 (5.8%, 3.0% to 9.9%) with diabetes. In each group, approximately half of these patients had symptoms of dyspnoea, and therefore had heart failure. Overall rates of heart failure, defined as symptoms of dyspnoea plus objective evidence of cardiac dysfunction (systolic dysfunction, atrial fibrillation, or clinically significant valve disease) were 16.0% (11.6% to 21.2%) in patients with previous myocardial infarction, 8.4% (5.6% to 12.0%) in those with angina, 2.8% (1.4% to 5.0%) in those with hypertension, and 7.7% (4.5% to 12.2%) in those with diabetes. CONCLUSION: Many people with ischaemic heart disease or diabetes have systolic dysfunction or heart failure. The data support the need for trials of targeted echocardiographic screening, in view of the major benefits of modern treatment. In contrast, patients with uncomplicated hypertension have similar rates to the general population.

Impact of heart failure and left ventricular systolic dysfunction on quality of life: a cross-sectional study comparing common chronic cardiac and medical disorders and a representative adult population.

BACKGROUND: Heart failure and left ventricular systolic dysfunction (LVSD) are increasingly common disorders, with outcomes worse than many cancers. Evidence-based therapies, such as ACE inhibitors and beta-blockers, improve prognosis and symptoms, and reduce healthcare expenditure. However, despite the high prevalence and malignant prognosis, few studies have reported the impact of heart failure and LVSD on overall quality of life and, more crucially, have not researched the elderly or those in the community. METHODS: All patients attending the Echocardiographic Heart of England Screening (ECHOES) study of the prevalence of heart failure and LVSD in the community were assessed by clinical history and examination, electrocardiogram and echocardiography, and also completed the SF36 health status questionnaire. Quality of life in patients found to have heart failure, LVSD, and other cardiac and medical conditions are compared with the randomly selected general population sample. Data are generalisable to the UK. RESULTS: 6162 people in the community were screened in the ECHOES study, of whom 5961 (97%) completed the SF36. The health perceptions of 3850 people aged 45 years or older selected randomly from the population were compared with those of 426 patients diagnosed as having definite heart failure. Those with heart failure had significant impairment of all the measured aspects of physical and mental health, in addition to declines in physical functioning. Significantly worse impairment was found in those with more severe heart failure by NYHA class: indeed, NYHA functional class was closely correlated to SF36 score. Patients with asymptomatic left ventricular dysfunction and patients rendered asymptomatic by treatment had similar scores to the random population sample. Those with heart failure reported more severe physical impairment of quality of life than people giving a history of chronic lung disease or arthritis, with less impact on mental health than patients reporting depression. CONCLUSIONS: Patients with heart failure have statistically significant impairment of all aspects of quality of life, not simply physical functioning. The physical (role and functioning) health burden was significantly greater than that suffered in other serious common chronic disorders, whether cardiac or other systems. Optimising treatment to improve NYHA class appears to improve perceptions of quality of life for patients with heart failure. Given the dramatic decline in quality of life with heart failure, this end-point should be a much more important target for healthcare interventions, especially treatments such as ACE inhibitors and beta-blockers that are shown to improve quality of life.