MICE or NICE? An economic evaluation of clinical decision rules in the diagnosis of heart failure in primary care.

BACKGROUND: Detection and treatment of heart failure (HF) can improve quality of life and reduce premature mortality. However, symptoms such as breathlessness are common in primary care, have a variety of causes and not all patients require cardiac imaging. In systems where healthcare resources are limited, ensuring those patients who are likely to have HF undergo appropriate and timely investigation is vital. DESIGN: A decision tree was developed to assess the cost-effectiveness of using the MICE (Male, Infarction, Crepitations, Edema) decision rule compared to other diagnostic strategies to identify HF patients presenting to primary care. METHODS: Data from REFER (REFer for EchocaRdiogram), a HF diagnostic accuracy study, was used to determine which patients received the correct diagnosis decision. The model adopted a UK National Health Service (NHS) perspective. RESULTS: The current recommended National Institute for Health and Care Excellence (NICE) guidelines for identifying patients with HF was the most cost-effective option with a cost of £4400 per quality adjusted life year (QALY) gained compared to a "do nothing" strategy. That is, patients presenting with symptoms suggestive of HF should be referred straight for echocardiography if they had a history of myocardial infarction or if their NT-proBNP level was ≥400pg/ml. The MICE rule was more expensive and less effective than the other comparators. Base-case results were robust to sensitivity analyses. CONCLUSIONS: This represents the first cost-utility analysis comparing HF diagnostic strategies for symptomatic patients. Current guidelines in England were the most cost-effective option for identifying patients for confirmatory HF diagnosis. The low number of HF with Reduced Ejection Fraction patients (12%) in the REFER patient population limited the benefits of early detection.

Precise evaluation of the Helmholtz equation for optical propagation.

A precise computational integration of the Helmholtz equation was performed for laser propagation of an electromagnetic wave with no approximations or linearization. This computation integration was performed using 64-bit processors. This is illustrated for a uniform monochromatic beam from a circular aperture that has a uniform intensity. It predicts many Arago spots and near-field intensity fluctuations for a large ratio of aperture size to wavelength and converges to the usual Airy pattern in the far field.

Mode of death in patients with newly diagnosed heart failure in the general population.

BACKGROUND: Early prognosis for incident (new) heart failure (HF) patients in the general population is poor. Clinical trials suggest approximately half of chronic HF patients die suddenly but mode of death for incident HF cases in the general population has not been evaluated. AIMS: To describe mode of death in the first six months after a new diagnosis in the general population. METHODS: Two-centre UK population-based study. RESULTS: 396 incident HF patients were prospectively identified. Overall mortality rates were 6% [3-8%], 11% [8-14%] and 14% [11-18%] at 1, 3 and 6months respectively. There were 59 deaths over a median follow-up of 10months; 86% (n = 51) were cardiovascular (CV) deaths. Overall, the mode of death was progressive HF in 52% (n = 31), sudden death (SD) in 22% (n = 13), other CV death in 12% (n = 7), and non-CV death in 14% (n = 8). On multivariable analysis, progressive HF deaths were associated with older age, lower serum sodium, systolic hypotension, prolonged QRS duration at baseline and absence of ACE inhibitor therapy at the time of discharge or death. CONCLUSION: Early prognosis after a new diagnosis of HF in the general population is poor and progressive HF, rather than sudden death, accounts for the majority of deaths.

Diagnostic criteria and adjudication process both determine published event-rates: the ACTION trial experience.

OBJECTIVE: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria. METHODS: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC. RESULTS: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228). CONCLUSION: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one.

The development of heart failure in patients with stable angina pectoris.

BACKGROUND: To describe the clinical characteristics of patients with stable angina pectoris who develop heart failure and the events preceding its onset. METHODS AND RESULTS: Of 7665 patients with stable angina in the ACTION trial, which compared long-acting nifedipine to placebo, 207 (2.7%) developed heart failure (HF) during a mean follow-up of 4.9 years. Those who developed HF were significantly (P<0.05) older, more often had diabetes, had a more extensive history of cardiovascular disease, lower ejection fractions, a higher serum creatinine and glucose, a lower haemoglobin, and were more often on blood pressure lowering drugs. A cardiac event or an intervention (n=155), a significant non-cardiac infection (n=19) or poor control of hypertension (n=12) preceded the development of HF in 186/207 cases (90%). There was no obvious precipitating factor in the remaining 21 patients (10%). Myocardial infarction increased the risk of the development of new HF within one week more than 100-fold. Nifedipine reduced the incidence of HF by 29% (P=0.015). CONCLUSIONS: The development of heart failure is uncommon in patients with stable angina, and even less so in the absence of an obvious precipitating factor.

Incidence and outcome of persons with a clinical diagnosis of heart failure in a general practice population of 696,884 in the United Kingdom.

BACKGROUND: There are few large population-based studies of the incidence and outcome of heart failure where the diagnosis of heart failure (HF) has been made by a General Practitioner (GP) in the community. METHODS: From the General Practice Research Database in the UK, we selected a population of 686,884 people 45 years or older. Incident cases of HF in 1991 were classified definite HF, possible HF, or a first prescription of diuretics without a diagnosis of HF. The population was followed for 3-year mortality. RESULTS: A total of 6478 patients had definite HF (mean age 77.2 years, 55.5% women), 14,050 had possible HF and 6076 persons were prescribed diuretics without a definite or possible diagnosis of HF. The overall incidence of definite HF was 9.3/1000 persons/year and of possible HF 20.2/1000 persons/year. Diuretics were prescribed for the first time for other reasons for 8.7 persons/1000/year. The incidence of HF was higher in men. The incidence of definite HF increased with age. Survival curves showed higher mortality rates in the first 3 months after the diagnosis of HF. One-year cumulative probability of death for patients with definite HF was 15.9 times higher in men and 14.7 times higher in women in comparison with the UK population. CONCLUSION: The diagnosis of HF by a GP successfully identifies patients at high risk of death, comparable to patients with HF identified by cardiologists on the basis of defined diagnostic criteria. HF is common in the general population, increases sharply with age, and has a poor prognosis.

The epidemiological enigma of heart failure with preserved systolic function.

BACKGROUND: Current epidemiological evidence suggests that the prevalence of preserved systolic function in patients with heart failure varies widely from 13 to 74%. This inconsistency suggests a lack of consensus as to what this condition really is and how it has been characterised for epidemiological studies. AIMS: In this review, we summarise and discuss the current understanding of the epidemiology of heart failure with preserved systolic function and the challenges that this raises. METHODS: Studies were identified from Medline and Embase Literature Database searches using the subject headings heart failure, diastolic heart failure, epidemiology, incidence, prevalence, diagnosis, prognosis and mortality. RESULTS: Sixty-one studies of congestive heart failure with preserved systolic function were reviewed. There is great diversity in the criteria used to determine whether heart failure is present, the patient population, the setting of the study and methods of evaluating left ventricular function. This makes epidemiological studies of prevalence, morbidity and mortality impossible to compare. CONCLUSIONS: The diagnosis of this syndrome might be better defined in terms of symptoms, elevated neuro hormones and impaired cardiac workload. This would allow accurate identification of cases so that further research could be conducted to measure outcome and assess therapeutic benefit.

Optimal filter for phase correction of anisoplanatism.

An optimal filter algorithm for adaptive optics provides a powerful method for phase correction for propagation through the Earth's turbulent atmosphere involving anisoplanatism. In the new algorithm the outward phase correction is the sum of the product of a weighting function (the optimal filter) and all the wave-front measurements at the pupil, greatly improving the Strehl ratio. Two simplified cases are presented for illustration: (1) a collimated beam traversing a layer of uniform isotropic turbulence (angle anisoplanatism) and (2) focus anisoplanatism. It compares favorably with tomographic techniques. The technique can be extended to the case of thick, strong turbulence in the far field of a subaperture of an adaptive optics system.

Haemoglobin concentration and prognosis in new cases of heart failure.

Anaemia is common in severe chronic heart failure and is reported to be a predictor of death. We investigated 552 patients (median age 76 years, range 29-95; 54% men [n=296]), in whom the duration of heart failure was sufficiently short that it would be unlikely to affect haemoglobin concentrations. By contrast with studies in established chronic heart failure, haemoglobin was not independently associated with prognosis when age and serum creatinine concentration were included in the analysis. The adverse effects of anaemia on survival might be a consequence of chronic heart failure rather than a separate process causing disease progression.