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.

Long term bradycardia by electrical pacing: a new method for studying heart rate reduction.

OBJECTIVE: The aim was to develop a method of inducing bradycardia on a chronic basis by electrical pacing and to study its effect upon myocardial capillarity in pigs. METHODS: Farm pigs were instrumented with Medtronic dual chamber telemetric pacemakers and two leads, either both atrial or one atrial and one ventricular. Bradycardia was achieved by linking pacing stimuli to endogenous atrial or ventricular events for the different electrode positions respectively, and monitored postoperatively for 4-5 weeks by implanted telemetric ECG devices. Myocardial capillary supply (lectin staining) and myocyte cross sectional areas were then estimated in sections of the left ventricle. RESULTS: Heart rates were reduced by 40-50 beats.min-1 at operation from a resting rate of 110(SEM 3) beats.min-1 in eight animals and bradycardia maintained upon recovery from anaesthesia for up to five weeks, with no obvious limitations for the animals. After this time, heart rates measured under anaesthesia were found to remain low for up to 2 h after pacing had been switched off. There was no evidence of myocyte hypertrophy, yet mean capillary density.mm-2 was significantly increased by pacing, from 1470(50) to 1734(82), p < 0.02. CONCLUSIONS: It is possible to produce primary heart rate reduction in the pig by a novel means of pacing on a chronic basis, leading to increased myocardial capillary supply without myocyte hypertrophy. This method can provide a basis for future investigations of the beneficial effects of heart rate reduction in the vascularly compromised heart.

Central haemodynamic changes during lower body positive pressure in patients with congestive cardiac failure.

Fifteen patients with moderately severe and severe chronic congestive heart failure were studied to determine the central haemodynamic results of short term increases in lower body positive pressure. Central haemodynamic variables were determined by Swan-Ganz thermodilution catheterisation and arterial cannulation. Graded increases in lower body positive pressure were applied to supine patients using Medical Anti-Shock Trousers (MAST). Increasing lower body positive pressure by 25 mm Hg and 55 mm Hg caused increases in mean right atrial pressure (6.0 to 13.2 to 17.9 mm Hg; p less than 0.001 and p less than 0.0001 respectively) and mean pulmonary artery pressure (26.8 to 35.5 to 41.3 mm Hg; p less than 0.05 and p less than 0.01 respectively). No significant changes were seen in left heart filling pressures or in pulmonary vascular resistance. Furthermore, there were no significant increases in indices of cardiac work (cardiac index, left ventricular stroke work index, right ventricular stroke work index or cardiac power output) despite the increased right heart filling pressures. These results show that in patients with longstanding severe congestive heart failure, short term increases in cardiac return may increase right heart pressures but do not appear to cause either beneficial or detrimental changes in left heart haemodynamic indices.

Effect of unrestricted activity on accuracy of ambulatory blood pressure measurement.

A validation study of the Takeda TM-2420 ambulatory blood pressure recorder was performed on 10 subjects using the Oxford ambulatory intra-arterial recording apparatus during unrestricted activity. Electronic linkage of the two recorders ensured simultaneous blood pressure readings, taken from opposite arms. Although there was close approximation of intra-arterial and automated sphygmomanometric recordings over the range of blood pressure encountered in this study, there was a wide scatter of points and a tendency for the machine to underestimate systolic pressure by more than 15 mm Hg in the hypertensive range (systolic blood pressure more than 160 mm Hg) was detected. These findings suggest that automated recording of blood pressure during unrestricted activity may have a proportion of artifactual readings. Although simultaneous intra-arterial blood pressure recording may not be appropriate for widespread use in device validation, this study illustrated some potential disadvantages of the current validation recommendations, namely, the absence of assessment of device accuracy during unrestricted and ambulatory activity.

Effect of quinapril on blood pressure and heart rate in congestive heart failure.

The effect of quinapril on blood pressure (BP), heart rate (HR) and their variabilities in 12 patients with severe congestive heart failure (New York Heart Association class III and IV) was assessed using ambulatory electrocardiographic and intraarterial monitoring. Mean +/- standard deviation daytime BP was 122/75 +/- 20/15 mm Hg at baseline and 113/70 +/- 13/16 mm Hg after 16 weeks of therapy with quinapril (p greater than 0.05 for systolic and diastolic BP); mean nighttime BP was 114/69 +/- 19/14 mm Hg at baseline and 107/69 +/- 15/14 mm Hg with quinapril (p greater than 0.05 for systolic and diastolic BP). Mean daytime HR was unchanged but nighttime HR was reduced from 77 +/- 11 to 71 +/- 10 beats/min, p = 0.02. HR variability (difference between the 75th and 25th percentiles of the frequency distribution of RR intervals) increased from 91 +/- 34 to 134 +/- 47 ms, p = 0.008. The variability of successive differences between RR intervals also increased significantly (75th to 25th percentile = 17 +/- 4 ms at baseline and 31 +/- 26 ms with quinapril, p = 0.02). Long-term quinapril caused clinically unimportant decreases in BP in patients with severe congestive heart failure. An increase in vagal activity caused by the reduction in circulating angiotensin II may account for the effect of converting enzyme inhibition on HR and its variability.

Acute and chronic hemodynamic effects of xamoterol in mild to moderate congestive heart failure.

Xamoterol, a new beta 1 partial agonist, has the potential to modulate cardiac response to variations in sympathetic tone in patients with heart failure. Its properties should result in beta-receptor stimulatory effects at low levels of sympathetic tone and beta-receptor protective effects at higher levels of sympathetic tone. The acute effects of intravenous (i.v.) xamoterol on hemodynamics at rest and during exercise were studied in 30 patients with mild to moderate heart failure (13 patients in New York Heart Association class II; 17 in class III) due to ischemic (n = 24) or cardiomyopathic (n = 6) heart disease. Cardiac index, stroke volume and stroke work index at rest were significantly improved after i.v. administration of xamoterol and consistent with net agonist effects. During exercise, heart rate and double product were significantly reduced (net antagonist effects), but with preservation of the expected increases in cardiac index and systolic blood pressure. These hemodynamic findings confirm the ability of xamoterol to modulate cardiac response to variations in sympathetic tone. Tachyphylaxis and arrhythmogenicity limit the chronic use of drugs with full beta-agonist properties as positive inotropes in heart failure. The patients were therefore entered into a 6-month double-blind, placebo-controlled, crossover study of chronic oral xamoterol therapy, 200 mg twice daily, and the hemodynamic responses to i.v. xamoterol were repeated at the end of the trial. No impairment in either resting or exercise effects was observed, indicative of a maintained response and absence of tachyphylaxis after chronic therapy. Furthermore, 24-hour ambulatory electrocardiographic monitoring showed no change in ventricular arrhythmias during oral treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Acadesine: a new drug that may improve myocardial protection in coronary artery bypass grafting. Results of the first international multicenter study. Multinational Acadesine Study Group.

The effect of acadesine, an adenosine-regulating agent, on the incidence of myocardial infarction, all adverse cardiovascular outcomes (myocardial infarction, cardiac death, left ventricular dysfunction, life-threatening arrhythmia, or cerebrovascular accident) and mortality was assessed in 821 patients undergoing coronary artery bypass grafting. Patients were prospectively stratified to a high-risk group (age > 70 years, unstable angina, previous coronary bypass, unsuccessful angioplasty, or ejection fraction < 30%) or a non-high-risk group. They were randomized in a double-blind manner to placebo (n = 418) or acadesine (n = 403) by intravenous infusion over 7 hours (0.1 mg/kg per minute) and in the cardioplegic solution (placebo or acadesine; 5 micrograms/ml). Acadesine did not significantly affect the incidence of myocardial infarction in the overall study population, but it significantly reduced the incidence of Q-wave myocardial infarction in high-risk patients (placebo, 19.7%; acadesine, 10.0%; p = 0.032). The incidences of all adverse cardiovascular outcomes (placebo, 19.4%; acadesine, 18.4%) and overall mortality (placebo, 3.4%; acadesine, 2.7%) were similar between the two treatment groups. However, acadesine reduced the incidence of cardiac related events that contributed to deaths occurring during the first 3 postoperative days so that the incidence of death in this period was lower (placebo, 1.9%; acadesine, 0.2%; p = 0.038). No adverse events were related to acadesine treatment. Although overall there were no statistically significant between-group differences for the primary study end points, a secondary analysis in a prospectively defined high-risk subgroup suggests that acadesine may be beneficial in some patients.

Is there a relationship between muscle fatigue resistance and cardiovascular responses to isometric exercise in mild chronic heart failure?

BACKGROUND: Exercise intolerance in chronic heart failure (CHF) may be due to altered fatigue resistance and muscle afferent input to the cardiovascular system from dysfunctional skeletal muscle. AIM: To determine whether calf muscle fatigue resistance was associated with the magnitude of a muscle afferent driven cardiovascular response to isometric exercise. METHODS AND RESULTS: Cardiovascular responses were recorded in eight stable CHF patients (ejection fraction 20-40%) and nine healthy, age-matched controls during voluntary and electrically evoked isometric plantar flexion and post-exercise circulatory occlusion. The force developed by the plantar flexors during a 2-min submaximal electrically evoked fatigue test was measured. There was no relationship between ischaemic muscle fatigue and cardiovascular changes during and after voluntary contraction in either group nor evoked contraction in the CHF group. In the control group, the change in diastolic blood pressure (DBP) at the end of evoked contraction was related to the severity of fatigue at 90 s and 120 s (FI=0.01DeltaDBP+0.3, r=0.81, P<0.05 and FI=0.02DeltaDBP+0.8, r=0.84, P<0.01, respectively). CONCLUSION: Muscle fatigue resistance did not relate to the magnitude of the cardiovascular stress generated by isometric exercise of the same muscle in these patients.

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.

Acute aortitis and aortic incompetence due to systemic rheumatological disorders.

We report the clinical, laboratory and echocardiographic features of five cases of aortic incompetence associated with ankylosing spondylitis, rheumatoid arthritis and undefined connective tissue diseases. Immunosuppression with steroids and cytotoxic agents was used to suppress aortic root inflammation in four cases; in three the aortic root size stabilized and the patients remain well with no evidence of increasing aortic incompetence. In one case, control of the inflammatory process was never fully achieved for any length of time and the patient died shortly after aortic valve replacement. A fifth case required urgent valve replacement and remains well. A systemic rheumatological disorder should be considered in cases of apparent "lone" aortic incompetence and conversely aortic incompetence should not be overlooked in established systemic rheumatological disease. Immunosuppressive therapy may prevent or delay the need for aortic valve replacement in such cases.

Serum cortisol levels predict infarct size and patient mortality.

We have investigated prospectively the serum cortisol response to acute myocardial infarction in 70 consecutive patients admitted to a coronary care unit and we have shown that the levels are significantly raised early in the course of the illness and prior to elevation of the cardiac specific enzyme fraction, creatine kinase MB. The magnitude of the cortisol response is related to the size of the ensuing infarction (rs = 0.54) as calculated from the total creatine kinase MB release (P < 0.001) and very high levels (> 2000 mumol/l) are predictive of mortality (P < 0.05). Serum cortisol levels may have a role in the early identification of myocardial infarction and in predicting those patients with a poor prognosis.

Results of surgical revascularization in ischaemic heart failure without angina.

Seventeen patients with severe ischaemic heart failure without angina were studied prospectively to determine the effects of surgical revascularization on exercise tolerance, peak oxygen consumption and left ventricular function at rest and during inotropic stimulation at 3 months after surgery. Suitability for surgery was assessed by the presence of ischaemia identified by thallium scintigraphy and stress electrocardiographic (ECG) testing and the left ventricular response to dobutamine measured by radionuclide ventriculography. One patient died awaiting surgery and one required cardiac transplantation. Fifteen patients underwent coronary artery surgery with two perioperative deaths. Thirteen patients were restudied 3 months after surgery. Mean treadmill exercise time (362 +/- 204 s to 562 +/- 303 s, P < 0.05) and peak oxygen consumption (14.9 +/- 3.5 ml/kg per min to 20.8 ml/kg per min, P < 0.01) increased significantly. Resting ejection fraction was not changed after surgery (20 +/- 5% to 21 +/- 6%) but ejection fraction during derived from thermodilution Swan-Ganz catheter data both at rest during dobutamine stimulation were unchanged after surgery. At 13 +/- 3 months after surgery there had been three sudden deaths and one patient had undergone successful cardiac transplantation. Of the remaining nine patients, three had improved to NYHA symptomatic class I, three were in NYHA class II and three in NYHA class III. Repeat treadmill exercise testing in seven patients showed that the improvement in exercise capacity evident in the first follow-up visit was maintained during long-term follow-up.

Tissue atenolol levels following chronic beta-adrenoceptor blockade using oral atenolol in dogs.

Tissue atenolol concentrations are high following chronic continuous beta-adrenoceptor blockade in dogs. Furthermore, significant concentrations of this poorly lipid soluble drug are found within the central nervous system after chronic dosing. It is suggested that all beta-adrenoceptor blocking agents may enter the central nervous system in significant and sufficient quantities to account for a central antihypertensive action of this group of compounds. Sequestration of beta-adrenoceptor agents in the CNS or other tissues may account for other clinically observed effects including adaptive effects.