Review article: the burden of illness of non-cardiac chest pain.

BACKGROUND: Non-cardiac chest pain is a common condition affecting approximately one-quarter of the population during their lifetime, but the long-term economic costs of non-cardiac chest pain are poorly defined. METHODS: A MEDLINE and Current Contents search was performed from 1991 to 2002 using specific keywords. All major articles on the subject of non-cardiac chest pain in this period were reviewed and their reference lists searched. RESULTS: Limited studies suggest that the majority of those with non-cardiac chest pain do not consult a doctor regarding their symptoms; the drivers of health care seeking are not known. The impact on the quality of life in consulters can be severe, with as many as 36% reporting much lower quality of life levels. The diagnosis of non-cardiac chest pain can be difficult due to the heterogeneous nature of the condition, with significant overlap of gastro-oesophageal reflux disease, chest wall syndromes and psychiatric disease, which may drive up the costs of management. The prognosis appears to be good, but there are conflicting results in long-term studies. CONCLUSIONS: The costs of non-cardiac chest pain to the health care system are likely to be large and represent a significant proportion of each Western country's health care budget. Further studies are required to determine methods of reducing health care costs.

Trends in pacemaker mode prescription 1984-1994: a single centre study of 3710 patients.

OBJECTIVE: To evaluate trends in pacemaker mode prescription from 1984 to 1994 with particular reference to the changes in pacemaker mode prescription for patients aged 80 years and older at implant. DESIGN: Prospective evaluation of indications for pacing and pacemaker mode prescription in all patients undergoing new pacemaker implantation from 1992 to 1994. Comparison with retrospectively obtained data for patients paced from 1984 to 1991. SETTING: Tertiary referral cardiothoracic centre. PATIENTS: Group 1: 2622 patients paced at one centre and entered into the national pacing database from 1984 to 1991. Group 2: 1088 consecutive patients paced from 1992 to 1994. RESULTS: Use of atrial (AAI) and dual chamber (DDD) pacemakers increased progressively in patients of all ages from 1984 to 1994. There was an increase in the proportion of patients aged 80 years and older from 25.4% (group 1) to 40.5% (group 2). Patients of all ages in group 2 were more likely to receive DDD units for atrioventricular block (odds ratio (95% confidence interval) (CI) 9.0 (7.0 to 11.5)) and AAI or DDD units for sinus node disease (odds ratio (95% CI) 11.0 (7.7 to 15.8)) than those in group 1. Elderly patients (age > or = 80 at implant) with atrioventricular block or sinus node disease and a suitable atrial rhythm were less likely to receive DDD or AAI pacemakers than younger patients in both groups. CONCLUSIONS: Use of atrial and dual chamber pacing modes has increased substantially in patients of all ages over the last decade. Although elderly patients represent an increasing proportion of the paced population, they remain less likely to receive atrial or dual chamber pacemakers than younger patients.

Drug treatment associated with heart valve replacement.

This article reviews a number of specific pharmacological considerations for patients with prosthetic heart valves. All patients with mechanical heart valves should be anticoagulated. In the past, an International Normalised Ratio (INR) of 2.5 to 4.5 has been recommended. Recent nonrandomised studies have suggested that a patient with a prosthetic valve who is at low risk for thromboembolic events could have an INR ranging from 1.8 to 3.5. The lower end of this range should only be used for patients at higher than average risk of haemorrhage, until randomised data show that levels below 2.5 may be applied universally. In high-risk patients (particularly those with previous thromboembolic events) low dose aspirin should be added. During noncardiac surgery, a patient at low risk for thromboembolic events could be managed by discontinuing anticoagulation 3 days before the operation, with warfarin recommenced as soon as possible afterwards. Perioperative heparinisation would be appropriate in a higher risk patient. Women with prosthetic heart valves wishing to become pregnant should be converted to the use of twice-daily subcutaneous heparin injections. Patients with bioprosthetic valves can be managed without anticoagulation unless they have some other reason to require it. Patients at high risk should be treated with aspirin or warfarin. Thrombolytic therapy for acute valve thrombosis should be used for those who are haemodynamically compromised and therefore have a high risk of mortality from operative intervention. All patients with prosthetic heart valves undergoing invasive procedures potentially causing bacteraemia should receive antibiotic prophylaxis for endocarditis. The actual drugs used depend on the likely nature of the bacteraemia, and any possible patient hypersensitivity.

The influence of myocardial systolic shortening on action potential duration following changes in left ventricular end-diastolic pressure.

INTRODUCTION: Contraction-excitation feedback may be an important factor in arrhythmogenesis in patients with heart failure. We have previously demonstrated the contrasting effects of raising left ventricular end-diastolic pressure on action potential duration in dog and guinea pig hearts. The current study was undertaken to assess whether these differing effects might reflect differences in the effect of varying left ventricular end-diastolic pressure on systolic shortening in the two models. METHODS AND RESULTS: Two models were studied and compared. In open chest dog hearts and isolated guinea pig hearts, measurements of myocardial segment length were made while left ventricular end-diastolic pressure was raised and lowered at constant left ventricular peak systolic pressure. Action potentials were also recorded while left ventricular end-diastolic pressure was changed. The dog hearts were studied further in a manner aimed at reproducing the contraction pattern of the guinea pig hearts. In the in situ dog heart, elevation of left ventricular end-diastolic pressure, and the consequent increase in end-diastolic segment length, was accompanied by a marked increase in systolic shortening, such that minimum systolic segment length remained unchanged. Elevation of left ventricular end-diastolic pressure was accompanied by a prolongation of action potential duration. In the in vitro guinea pig model, elevation of left ventricular end-diastolic pressure was accompanied by more modest changes in systolic shortening, which were not sufficient to compensate for increased diastolic segment length. Consequently, minimum systolic segment length increased as the hearts dilated. Elevation of left ventricular end-diastolic pressure was accompanied by a shortening of action potential duration. In a further series of experiments, the effects of increased left ventricular end-diastolic pressure were studied in the dog model while allowing aortic pressure to rise, thereby restricting systolic shortening. Under these circumstances, the dog model was similar to the guinea pig model, with an increase in left ventricular end-diastolic pressure causing a shortening of action potential duration. CONCLUSION: Our results suggest that the effects of preload changes on action potential duration depend on accompanying changes in systolic shortening. This suggests a possible role for contraction-excitation feedback in arrhythmogenesis in patients with regional wall-motion abnormalities.

The use of a microcomputer to automate measurement of action potential duration for both transmembrane and monophasic action potentials.

Measurement of action potential duration is made more valuable if it can be made simultaneously with other variables, to which it may be related. We have developed a microcomputer-based system which allows measurement of action potential duration, both for transmembrane action potentials and for monophasic action potentials. The system allows simultaneous recording and analysis of action potentials and intraventricular pressures. Both end-diastolic and maximum systolic pressures have been analysed. Action potential duration was assessed at four different levels of the repolarization curve. We have analysed the consistency of measurements made by the computer, and compared them to measurements made manually, using results from six dog experiments. For action potential duration, there was no systematic difference between the manual and the computer methods, but the computer was significantly more consistent. In the case of the pressure measurements, the two methods were approximately the same in their consistency, and again there was no systematic difference. We have demonstrated that potential errors in determination of the average diastolic potential did not significantly affect the results obtained by our method. The variances of action potential duration measurements made at different levels of repolarization were equal. We demonstrated that there was no effect of amplitude on the action potential duration of potentials recorded under steady-state conditions.

The effects of ventricular end-diastolic and systolic pressures on action potential and duration in anaesthetized dogs.

1. Although it is known that mechanical events in the heart influence the duration of the cardiac action potential, there is no quantitative information on the effects of independent changes in ventricular end-diastolic and systolic pressures. 2. Experiments were carried out on open-chest anaesthetized dogs in which the autonomic nervous influences on the heart were prevented and monophasic action potentials were recorded form the epicardial surface of the left ventricle. The duration of these action potentials was taken as the interval from the upstroke to the point of 90% repolarization. 3. Elevation of left ventricular peak systolic pressure, at constant end-diastolic pressure, significantly shortened the monophasic action potential. 4. Elevation of end-diastolic pressure at constant peak systolic pressure significantly lengthened the monophasic action potential. 5. Responses were not dependent on release of noradrenaline from sympathetic nerve terminals because they persisted after administration of bretylium tosylate. They were also not due to myocardial ischaemia because they persisted when coronary perfusion pressure was maintained at a constant high level. 6. Simultaneous recordings of changes in myocardial segment length showed the expected responses to changes in ventricular pressures: increases in shortening in response to increases in diastolic pressure and no consistent effect from changes in systolic pressure. 7. These investigations demonstrate the independent effects of changes in systolic and end-diastolic pressures on cardiac action potential duration. This effect is likely to be an effect of the mechanical events, i.e. contraction-excitation feedback. This response may be mediated through changes in myocardial fibre tension, the consequent changes in fibre shortening, or both.

Contraction-excitation feedback in an ejecting whole heart model--dependence of action potential duration on left ventricular diastolic and systolic pressures.

STUDY OBJECTIVE: Contraction-excitation feedback may play a role in arrhythmogenesis in heart failure. The aims of this study were to determine whether contraction-excitation feedback has a significant effect on action potential duration within a physiological range of pressures, and to investigate the individual effects of left ventricular end diastolic and peak systolic pressures on action potential duration. DESIGN: A new model was developed for studying contraction-excitation feedback in a physiologically ejecting isolated heart preparation. Hearts were perfused via the left atrium, ejecting against an aortic afterload. By varying left atrial and aortic pressures, left ventricular end diastolic pressure and left ventricular peak systolic pressure were controlled independently. Intracellular potentials were recorded from the epicardium. EXPERIMENTAL MATERIAL: Hearts (n = 33) were obtained from guinea pigs weighing 300-350 g. MEASUREMENTS AND MAIN RESULTS: Increasing left ventricular end diastolic pressure from 0.3 to 1.1 kPa (2.2 to 8.3 mm Hg), at constant left ventricular peak systolic pressure, shortened action potential duration by 11.3(SEM 1.5) ms (p less than 0.0005). Action potential duration achieved a new steady state within 30 s of a change in end diastolic pressure. The changes were fully reversible. The effects of left ventricular peak systolic pressure variation at constant left ventricular end diastolic pressure were less marked. Increasing left ventricular peak systolic pressure from 10.3 to 13.1 kPa (75 to 100 mm Hg) shortened action potential duration by 2.1(0.7) ms (p less than 0.01). Reduction of aortic pressure below 8 kPa had variable effects on action potential duration, reflecting the development of ischaemia. CONCLUSION: The results show the existence of contraction-excitation feedback in a physiologically ejecting whole heart preparation and suggest that raised end diastolic pressure may contribute to arrhythmogenesis in heart failure.

Antiarrhythmic therapy and survival following myocardial infarction.

Arrhythmias remain a major cause of late mortality following myocardial infarction. They arise due to fibrosis within the infarct, which creates the conditions of slow conduction necessary for re-entry. In individual patients who have already manifested a malignant arrhythmia, antiarrhythmic drug therapy, guided by invasive electrophysiological testing, is of proven benefit in prolonging survival. By contrast, when used on a population basis, antiarrhythmic drug therapy has proved singularly ineffective. This is illustrated by the recent Cardiac Arrhythmia Suppression Trial (CAST) study--far from improving survival, antiarrhythmic therapy increased mortality. The use of antiarrhythmic drugs on a population basis is therefore fundamentally flawed. Hemodynamic intervention provides an alternative strategy in arrhythmia prevention. Hemodynamic changes may influence electrophysiological parameters and arrhythmogenesis in a number of ways. First, myocardial stretch may contribute to arrhythmogenesis through contraction-excitation feedback. Second, hemodynamic changes can influence ventricular remodeling following infarction, which may be an important determinant of subsequent arrhythmogenesis. Hemodynamic intervention, therefore, represents a promising new approach to arrhythmia prevention following myocardial infarction.