Biomedical subjects
Publications and source records attributed to J C Cowan.
The evidence base for implantable cardioverter-defibrillator (ICD) therapy requires expansion of guidance/indications to allow UK physicians to treat a broader range of patients. The ICD clinical consultees to the National Institute for Health and Clinical Excellence (NICE) review current guidance/guidelines, explain the evidence base, and suggest a UK ICD implantation strategy.
A 14-year-old girl with right ventricular dysplasia and recurrent drug refractory ventricular tachycardia underwent thoracoscopic mapping cryoablation. Good access to the right ventricular free wall was obtained. We suggest this technique may have an important role in the management of patients with right ventricular tachycardia.
OBJECTIVE: To explore the current use of secondary preventive treatment in survivors of out of hospital cardiac arrest without myocardial infarction (primary ventricular tachycardia/ventricular fibrillation (VT/VF)) in West Yorkshire, and assess the implications of recent studies on the benefits of implantable cardioverter-defibrillators (AICD) in this context. DESIGN: Retrospective analysis of an ambulance service based database of outcome after resuscitation of out of hospital cardiac arrest and the Leeds AICD implantation database. MAIN OUTCOME MEASURES: Mortality, rate of referral for specialist investigation, antiarrhythmic treatment. RESULTS: Twelve month mortality following successful discharge after primary VF arrest was 15%. Of 53 patients with primary VF/VT, 29 apparently did not see a cardiologist during the initial admission. Amiodarone was the most widely used antiarrhythmic agent. Six patients (15%) received an AICD. During the same period 22 patients from the same catchment area received an AICD following an in-hospital cardiac arrest. CONCLUSIONS: Mortality among survivors of non-infarct related prehospital cardiac arrest remains significant, with few patients being referred for specialist investigation. The implementation of recent guidelines on AICD use in cardiac arrest survivors would have resulted in an approximate 60% increase in the total numbers of defibrillators implanted in the West Yorkshire area.
In a cohort of 67 patients from the Acute Infarction Ramipril Efficacy study, we showed that ramipril therapy was associated with a significant reduction in QT dispersion over a 2-month period after acute myocardial infarction. This reduction of ventricular repolarization inhomogeneity indicates an antiarrhythmic effect and may be an important additional mechanism for the reduced all-cause mortality and sudden death incidence achieved with angiotensin-converting enzyme inhibition after acute myocardial infarction.
BACKGROUND: QT interval dispersion is a marker of inhomogeneous ventricular repolarization, and therefore has the potential to predict re-entry arrhythmias. Following acute myocardial infarction, increased QT dispersion has been associated with a higher risk of ventricular arrhythmias. However, whether or not QT dispersion predicts prognosis post-acute myocardial infarction is not clear. We addressed this issue by analysing the AIREX study registry. METHODS: AIREX was a follow-up study of 603 post-acute myocardial infarction patients who exhibited clinical signs of heart failure and were randomly allocated to ramipril or placebo. An interpretable 12-lead ECG obtained between day 0 and day 9 after the index infarction (median time 2 days) was available in 501 patients. We examined whether QT dispersion was a predictor of all-cause mortality in the AIREX study registry (mean follow-up 6 years). RESULTS: QT dispersion measurements were significantly increased in patients who subsequently died (QT dispersion: 92.0 +/- 38.5 ms vs 82.7 +/- 34.3 ins. P=0.005; rate corrected QT dispersion: 105.7 +/- 42.7 ms vs 93.1 +/- 35.9 ms, P<0.001). Univariate analysis showed that QT dispersion as a predictor of all-cause mortality risk (QT dispersion: hazard ratio per l0 ms 1.05, [95% CI 1.02 to 1.09]. P= 0.004; rate corrected QT dispersion: 1-07 [1.03 to 1.10], P<0.001): an increase of 10 ms added a 5-7%, relative risk of death. QT dispersion remained an independent predictor of all-cause mortality risk on multivariate analysis (QT dispersion: 1.05 [1.01 to 1.09], P=0.027; rate corrected QT dispersion: 1.05 [1.01 to 1.09]. P=0.022). CONCLUSION: QT dispersion. measured from Li routine 12-lead ECG following acute myocardial infarction complicated by heart failure provides independent information regarding the probability of long-term survival. However. the low sensitivity of this electrocardiographic marker limits its usefulness for risk stratification if used in isolation.
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OBJECTIVE: To assess the possible benefits of intravenous isosorbide dinitrate in acute myocardial infarction and oral isosorbide mononitrate in subacute myocardial infarction. METHODS: 316 patients presenting with acute myocardial infarction were entered into double blind placebo controlled clinical trials assessing infarct size by enzyme release, ventricular size and function by echocardiography, reperfusion by continuous 12 lead ST segment monitoring and late potentials by high resolution electrocardiography. RESULTS: 301 patients, of whom 292 (97%) received thrombolytic treatment, were randomised on admission to intravenous isosorbide dinitrate or placebo. Overall, there was no significant effect of treatment on infarct size, ST segment resolution, ventricular remodelling, or late potentials at day 3. A trend was observed towards a reduction in infarct size in patients with non-Q wave infarction treated with isosorbide dinitrate. Heterogeneity of nitrate effect was observed in relation to the degree of ST segment elevation on presentation with a clear benefit of isosorbide dinitrate in patients with moderate ST segment elevation (472 U/l v 704 U/l, P = 0.003) and a trend towards a deleterious effect in patients with marked ST segment elevation (1152 U/l v 1058 U/l, P = 0.2). ST segment re-elevation was more common among patients receiving nitrate treatment than in those assigned to placebo (29 v 16, P < 0.05). Some 160 patients underwent a further randomisation to sustained release isosorbide mononitrate or placebo on day 3. Echocardiographic volumes after 6 weeks of treatment were similar in the two groups. CONCLUSIONS: No benefit was observed with administration of nitrates in the treatment groups as a whole for either acute or subacute infarction. There was, however, evidence of heterogeneity of effect in the different subgroups of acute infarction, and the possibility that nitrates may have differing actions in different groups of patients should be considered.
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In addition to well-established roles in the management of stable angina, unstable angina and heart failure, nitrates are widely used in the management of acute infarction and the subacute period of recovery after infarction. A meta-analysis suggested that intravenous nitrate therapy in acute infarction reduced mortality by 35%. Subsequently, two recently reported 'mega' trials, GISSI-3 and ISIS-4, addressed the role of nitrates during and after infarction. The results of the mega trials have failed to substantiate a statistically significant benefit for nitrates. The contrast between the promising results of the meta-analysis and the disappointing results of the mega trials raises a number of issues considered in this paper. The role of nitrates in acute myocardial infarction remains unclear. The mega trials do offer some suggestive evidence of an early benefit of nitrate therapy. If any benefit does exist, it must be much smaller than the 35% reduction in mortality suggested by the meta-analysis. Further trials are required to assess the possibility of an early acute benefit. Any benefits will probably apply only to subgroups of infarcts.
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.
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.
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BACKGROUND: Arrhythmias are common in patients who have developed ventricular enlargement after myocardial infarction. METHODS AND RESULTS: A prospective study was undertaken to assess the relation between ventricular dilatation and the development of late potentials after myocardial infarction. Echocardiograms and signal-averaged ECGs were recorded on days 1,3,7, and 42 in 52 patients with a first anterior myocardial infarction. Twenty-nine percent of patients were late potential-positive on their initial signal-averaged ECG recorded on the day of admission. The incidence of late potentials rose during the next week to a peak of 42% at day 7, declining to 13% by day 42. The presence of late potentials on the day of admission was associated with an increase in end-diastolic volume index of 16.1 +/- 6.0 mL/m2 (mean +/- SEM), compared with a decreased of 4.7 +/- 2.7 mL/m2 among late potential-negative patients (P < .006). Qualitatively similar results were evident for late potentials on day 3 and day 7. By contrast, there was no association between late potentials on day 42 and ventricular dilatation. Marked dynamic changes in late potentials were evident during the first week. Patients with persistent late potentials (n = 9) on all three recordings in the first week showed a marked increase in end-diastolic volume index of 21.3 +/- 8.1 mL/m2 (P < .005 in comparison with patients who were persistently negative [n = 20]). Patients demonstrating dynamic positivity (n = 15) not present on all three recordings in the first week showed no significant increase in end-diastolic volume index. CONCLUSION: It is concluded that late potentials during the first week after infarction are associated with subsequent ventricular dilatation. These early-phase late potentials may be a manifestation of cell slippage. They arise before gross topographical enlargement and may serve as a predictor of ventricular dilatation.
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.