Search

Patient referrals from general practice for suspected heart failure are increasing the demand for echocardiograms, many of which are normal. We investigated whether general practitioners could be more selective by referring only patients with abnormal electrocardiograms for echocardiography. The electrocardiograms of 200 patients attending a heart failure clinic were analysed by a consultant cardiologist and two general practitioners. All three assessors examined the electrocardiograms independently and unaware of the echocardiography results. The correlation between abnormal electrocardiograms and left ventricular systolic dysfunction on echocardiography was assessed, together with the concordance between the assessors in their electrocardiogram interpretations. One hundred and sixty-five patients had echocardiographic evidence of left ventricular systolic dysfunction. When interpreted by a cardiologist, the electrocardiogram had a sensitivity of 89.1% and a specificity of 45.7% in predicting left ventricular systolic dysfunction. The general practitioners' results were comparable to the cardiologist's. We estimate that using the electrocardiogram to select patients could reduce the number of open access echocardiograms performed for suspected heart failure by up to 43% but would miss 10% of those with significant left ventricular systolic dysfunction. We therefore do not recommend selecting patients for open access echocardiography on the basis of electrocardiographic abnormalities.

Background: Drugs that improve symptoms in patients with heart failure must also be assessed for their effects on survival. Ibopamine stimulates DA-1 and DA-2 receptors and causes peripheral and renal vasodilatation; the drug improves symptoms of heart failure. We assessed the effect of ibopamine on survival in patients with advanced heart failure in a multicentre, randomised placebo-controlled study., Methods: Patients with advanced severe heart failure (New York Heart Association classes III and IV) and evidence of severe left-ventricular disease, who were already receiving optimum treatment for heart failure, were randomly allocated oral ibopamine 100 mg three times daily or placebo. The primary endpoint was all-cause mortality. The study was designed to recruit 2200 patients, and the minimum duration of treatment would be 6 months. We did intention-to-treat and on-treatment analyses; a post-hoc subgroup analysis was also done., Findings: After we had recruited 1906 patients the trial was stopped early, because of an excess of deaths among patients in the ibopamine group. 232 (25%) of 953 patients in the ibopamine group died, compared with 193 (20%) of 953 patients in the placebo group (relative risk 1.26 [95% CI 1.04-1.53], p = 0.017). The average length of follow-up was 347 days in the ibopamine group and 363 days in the placebo group. In multivariate analysis, only the use of antiarrhythmic drugs at baseline was a significant independent predictor of increased fatality in ibopamine-treated patients., Interpretation: Ibopamine seems to increase the risk of death among patients with advanced heart failure who are already receiving optimum therapy, but the reasons for this increase are not clear. Our finding that antiarrhythmic treatment was a significant predictor of increased mortality in ibopamine-treated patients may be important, but exploratory analyses must be interpreted with caution.

Background: To determine whether specific angiotensin II receptor blockade with losartan offers safety and efficacy advantages in the treatment of heart failure over angiotensin-converting-enzyme (ACE) inhibition with captopril, the ELITE study compared losartan with captopril in older heart-failure patients., Methods: We randomly assigned 722 ACE inhibitor naive patients (aged 65 years or more) with New York Heart Association (NYHA) class II-IV heart failure and ejection fractions of 40% or less to double-blind losartan (n = 352) titrated to 50 mg once daily or captopril (n = 370) titrated to 50 mg three times daily, for 48 weeks. The primary endpoint was the tolerability measure of a persisting increase in serum creatinine of 26.5 mumol/L or more (> or = 0.3 mg/dL) on therapy; the secondary endpoint was the composite of death and/or hospital admission for heart failure; and other efficacy measures were total mortality, admission for heart failure, NYHA class, and admission for myocardial infarction or unstable angina., Findings: The frequency of persisting increases in serum creatinine was the same in both groups (10.5%). Fewer losartan patients discontinued therapy for adverse experiences (12.2% vs 20.8% for captopril, p = 0.002). No losartan-treated patients discontinued due to cough compared with 14 in the captopril group. Death and/or hospital admission for heart failure was recorded in 9.4% of the losartan and 13.2% of the captopril patients (risk reduction 32% [95% CI -4% to + 55%], p = 0.075). This risk reduction was primarily due to a decrease in all-cause mortality (4.8% vs 8.7%; risk reduction 46% [95% CI 5-69%], p = 0.035). Admissions with heart failure were the same in both groups (5.7%), as was improvement in NYHA functional class from baseline. Admission to hospital for any reason was less frequent with losartan than with captopril treatment (22.2% vs 29.7%)., Interpretation: In this study of elderly heart-failure patients, treatment with losartan was associated with an unexpected lower mortality than that found with captopril. Although there was no difference in renal dysfunction, losartan was generally better tolerated than captopril and fewer patients discontinued losartan therapy. A further trial, evaluating the effects of losartan and captopril on mortality and morbidity in a larger number of patients with heart failure, is in progress.

Treatment with angiotensin converting enzyme inhibitors confers significant morbidity and mortality benefits in patients with heart failure, yet previous studies have repeatedly shown that these drugs are underutilised in general practice. To investigate why this is the case, we conducted an anonymous questionnaire survey of 515 general practitioners in the Nottingham Health District. The response rate was 60.2%. We found that although 39.3% of respondents underestimated the poor prognosis associated with heart failure, 98% were aware of the prognostic benefits conferred by angiotensin converting enzyme inhibitors. However, 46.3% of respondents expressed concern about the potential adverse effects associated with angiotensin converting enzyme inhibitors, the main fears being hypotension and renal impairment. General practitioners who were concerned about adverse effects were significantly less likely to have initiated an angiotensin converting enzyme inhibitor for heart failure than those who were not (P<0.01). Further research is needed to identify which patients can safely be commenced on angiotensin converting enzyme inhibitors in general practice. In the meantime, general practitioners should be encouraged to refer patients whenever they are concerned about initiating angiotensin converting enzyme inhibitors in the community.

The cause of the breathlessness and reduced exercise capacity that occur in patients with chronic heart failure remains obscure. We examined the hypothesis that airway obstruction and bronchial hyper-responsiveness, which are recognised features of chronic heart failure, might contribute to the breathlessness and reduced exercise capacity in this condition. We studied 37 patients (7 female) with chronic heart failure, of mean age 61 years. Each patient underwent: (i) lung function testing with spirometry and expiratory flow volume loops. (ii) Measurement of bronchial responsiveness to methacholine. (iii) Symptom-limited treadmill exercise capacity using both incremental and fixed workload protocols, with measurement of Borg scores for breathlessness. Lung function was not significantly related to either exercise time, or Borg symptom scores in either exercise protocol. Bronchial hyper-responsiveness to methacholine was demonstrated in 12 patients. Exercise time did not correlate with the degree of bronchial hyper-responsiveness in these 12 patients. Group mean exercise time and Borg scores were not significantly different in these 12 patients when compared to the 25 patients in whom bronchial hyper-responsiveness was not found. We conclude that airway obstruction and bronchial hyper-responsiveness are not likely to be important determinants of reduced exercise capacity and breathlessness in chronic heart failure.

Although many methods exist to assess the degree of incapacity of patients with chronic heart failure during normal daily activities, all have their limitations. In this study we describe a new shoe-mounted pedometer and compare it with body worn pedometers in normal volunteers and in patients with chronic heart failure. Ten young normal healthy volunteers participated in a comparison of the new shoe-mounted device with body born pedometers and counting a direct footfall. Seventeen patients with chronic heart failure and 10 aged-matched healthy elderly subjects participated in a comparison of both pedometers over 7 days. In the young volunteers the shoe-mounted pedometers were more accurate than the body-borne devices. With both pedometers the patients with chronic heart failure had a reduced level of activity compared with the normal volunteers over the 1 week period (P = 0.01). In both the patients and volunteers the shoe-mounted device recorded a higher score than the body borne pedometers (P < 0.01). The electronic shoe mounted pedometers are a more accurate way of assessing customary activity. In patients with chronic heart failure customary activity is substantially reduced compared with fit healthy elderly subjects.

Ninety-five patients with suspected acute myocardial infarction were randomly allocated on admission to hospital on a double blind basis to treatment with lorcainide, a Class 1C anti-arrhythmic drug, or matching placebo. Treatment was continued for 6 weeks. Twenty-four-hour ECG tape recordings were made immediately on admission, on the sixth or seventh day after admission, and again just before the end of the treatment period. Lorcainide was shown to be an effective anti-arrhythmic agent. The study was not designed to evaluate the effect of lorcainide on survival, but there were nine deaths among the 49 patients treated with lorcainide compared with only one in the patients given placebo. These findings are consistent with the results of the First and Second Cardiac Arrhythmia Suppression trials (CAST and CAST-II). This study was carried out in 1980 but was not published at the time: it now provides an interesting example of 'publication bias'.

One hundred-thirty five patients with moderate heart failure, recruited from 18 centres, were included in a double blind, placebo controlled study to evaluate the effects of flosequinan on symptom limited tread-mill exercise tolerance. Fifteen patients in the placebo group were withdrawn from the study compared with 14 from the group given flosequinan. New York Heart Association classification was improved at week 16 in the flosequinan group relative to those randomised to placebo (P < 0.01). Depending how the other results are analysed flosequinan either appeared to have no effect on symptom limited exercise tolerance in those who completed the study; a suggestion of superiority if an analysis at endpoint is used (P = 0.09), or, if a covariate analysis at endpoint is used, then a significant improvement can be demonstrated (P = 0.04). Subset analysis suggests that the aetiology of the heart failure and the dose of diuretics used might have a major effect on the response to treatment. The best way of analysing clinical trials in heart failure is not clear as the results can be profoundly influenced by the way data from withdrawn patients are handled. The aetiology and diuretic requirement of patients may influence their response to treatment.

The exercise capability of 39 patients with severe chronic heart failure was assessed in several ways and compared with measurements of cardiac output. The relation between cardiac index and exercise tolerance measured on a treadmill was poor (r = 0.191, p = 0.245). However, exercise tolerance measured with a series of self-paced corridor walk tests showed moderate correlations with cardiac index (r = -0.404, p = 0.015 to r = -0.516, p = 0.001) and customary activity assessed by step counting correlated better with cardiac index (r = 0.537, p less than 0.001). Cardiac output therefore seems to be a factor determining patients' exercise capability when they choose their own walking speed but not when they undergo formal treadmill tests in the laboratory.

Ten patients with severe heart failure, symptomatic despite treatment with diuretics and captopril, completed a study of the effect of adding enoximone to their normal treatment. Enoximone or matching placebo was given for 4 weeks in randomized double-blind order following a single-blind placebo run-in period. Exercise capability was measured with two different treadmill protocols, a corridor walk test and by step-counting with body-worn pedometers. Cardiac output and limb blood flow were assessed non-invasively by measuring respiratory gases and by venous occlusion plethysmography. Measurements were made at rest and in response to treadmill exercise. The mean exercise tolerance measured using the modified Bruce treadmill protocol was increased from the placebo value (498 +/- 91 seconds) after both 2 weeks (573 +/- 94 seconds, P = 0.051) and 4 weeks of enoximone (572 +/- 100 seconds, P = 0.057). Enoximone increased exercise duration in fixed workload tests from the placebo value (252 +/- 75 seconds) after 2 weeks' treatment (431 +/- 98 seconds, P = 0.011) and after 4 weeks (381 +/- 85 seconds, (P = 0.01). The percentage improvement with the fixed workload test was greater than with the modified Bruce protocol at week 2 (P = 0.03) and at week 4 (P = 0.051). Enoximone increased the speed of walking 100 m at self-selected slow, normal and fast paces. It had little effect on customary activity of the patients. Enoximone increased cardiac output measured at rest and during submaximal exercise (P = 0.001). It also improved blood flow to the calf muscle at rest and after exercise (P = 0.01). Enoximone has a beneficial effect in chronic heart failure symptomatic despite treatment with diuretics and captopril. The magnitude of its effect, however, depends upon the technique used to assess it.

Ten patients with moderate heart failure who still had symptoms despite 40 mg frusemide daily were treated with increased doses of frusemide and the addition of captopril in randomised order. Four different methods were used to assess the patients' response to treatment. Both treatments improved symptom-limited exercise tolerance, higher-dose frusemide having a more favourable effect. Perceived exertion during submaximal exercise was reduced by similar amounts by both treatments. The time taken to walk 100 m at a self-selected slow speed was reduced by both treatments; again higher-dose frusemide had a more beneficial effect. The higher dose of frusemide also had a more favourable effect on visual analogue scores for dyspnoea, fatigue, and general well-being.

Forearm venous tone was measured throughout pregnancy in 68 nulliparous women thought to be at high risk of the development of gestational hypertension. Normotensive pregnancy was associated with a progressive venodilatation. Gestational hypertension subsequently developed in 12 women. Before the onset of hypertension, these 12 women showed a greater degree of venodilatation, compared with women who remained normotensive throughout their pregnancies (p less than 0.001). As the hypertension became manifest, the women became relatively venoconstricted (p less than 0.001). Simple, noninvasive measurements of forearm venous tone provide important information about the pathophysiology of gestational hypertension and may be useful in the detection of women who are at increased risk.

Limb blood flow and respiratory function were compared in ten patients with severe heart failure inadequately controlled by diuretics and normal control subjects matched for age and sex. Both forearm and calf blood flow, at rest and after exercise, were lower in the patients than in the control subjects. Oxygen consumption during submaximal exercise was also lower in the patients and minute ventilation was higher. Captopril, administered in a single-blind controlled study to the patients, resulted in an improvement in these abnormalities, with the exception of oxygen consumption. It also improved exercise tolerance and reduced perceived exertion during exercise. Captopril is effective treatment for severe heart failure and improves some of the peripheral haemodynamic and respiratory abnormalities.

Cardiac output was measured in ten patients at routine cardiac catheterisation and three patients with severe heart failure by means of a carbon dioxide rebreathing technique with a computer-assisted mass spectrometer and compared with cardiac output measured by thermodilution. There was a close correlation (r = 0.96, p less than 0.01) between the two methods. Cardiac output measured by the carbon dioxide rebreathing technique increased after a typical Christmas lunch by a mean of 1.6 1/min in a group of healthy volunteers.

The effects of enoximone, a new cyclic adenosine monophosphate phosphodiesterase inhibitor, were compared with those of captopril in a double-blind study in a group of 10 patients with severe heart failure. Four weeks treatment with enoximone improved symptom-limited exercise tolerance from a mean value of 11.33 to 13.36 minutes (P less than 0.05) and 4 weeks of captopril treatment from 11.01 to 13.92 minutes (P less than 0.05). Four of the patients had a greater exercise tolerance taking enoximone, the remaining 6 while taking captopril. Both drugs reduced perceived exertion during submaximal exercise. Minute ventilation measured at rest and during submaximal exercise was also reduced by both drugs. Resting and post exercise calf blood flow was increased to a similar extent with captopril (P less than 0.03) and enoximone (P less than 0.005). There was no difference in calf blood flow and calf vascular resistance between the drugs suggesting that the peripheral haemodynamic effects of enoximone are due to peripheral vasodilatation. Enoximone is a useful drug for the treatment of patients with severe heart failure.