Risk of sudden death after discharge following myocardial infarction.
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Death, Sudden, Cardiac↗
Biomedical subjects
S M Cobbe
Publications and source records attributed to S M Cobbe.
Task Force on Sudden Cardiac Death of the European Society of Cardiology.
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Algorithms↗
Effects of intravenous dofetilide on induction of atrioventricular re-entrant tachycardia.
OBJECTIVE: To assess the efficacy and safety of intravenous dofetilide in preventing induction of atrioventricular re-entrant tachycardia. DESIGN: A multicentre, open, dose ranging trial. Fifty one patients with electrically inducible atrioventricular re-entrant tachycardia were allocated to one of five doses of dofetilide (1.5, 3, 6, 9, and 15 microgram/kg), two thirds of the dofetilide dose being given over a 15 minute loading period and the remainder over a 45 minute maintenance period. MAIN OUTCOME MEASURE: Responders were defined as patients in whom dofetilide prevented reinduction of atrioventricular re-entrant tachycardia at the end of the infusion. RESULTS: Intravenous dofetilide had no effect on tachycardia inducibility at the two lower doses (1.5 and 3 microgram/kg) but prevented the reinduction of tachycardia at the three higher doses (6, 9, and 15 microgram/kg) at a rate of 36% (11/31). There was a clear relation between plasma dofetilide concentrations and efficacy (p = 0.009). In non-responders, dofetilide increased the cycle length of induced atrioventricular re-entrant tachycardia. Dofetilide increased the atrial and ventricular effective refractory periods, as well as the antegrade and retrograde effective refractory period of the accessory pathway. Treatment related side effects were reported in four patients, one with a new sustained incessant supraventricular tachycardia. CONCLUSIONS: Dofetilide shows promise as an agent for the prevention of atrioventricular re-entrant tachycardia in patients without structural heart disease.
Adolescent↗
Heterogeneous changes in action potential and intracellular Ca2+ in left ventricular myocyte sub-types from rabbits with heart failure.
OBJECTIVE: Myocardial cellular electrophysiology and intracellular Ca2+ regulation are altered in heart failure. The extent of these changes may vary within the layers of the ventricular wall. To examine this, cell size, action potential and intracellular Ca2+ transient characteristics (Fura-2) were measured in single cardiac myocytes from sub-epicardial, mid-myocardial, and sub-endocardial regions of the left ventricle of rabbits with heart failure. METHODS: Myocytes were isolated from animals with heart failure induced by chronic coronary artery ligation and from sham operated controls. Trans-membrane potential was measured using high resistance microelectrodes electrodes (30 M omega; 2 M KC1). Fura-2 was loaded into cells by incubation with the AM form. Subsequent fluorescence measurements were used to measure intracellular Ca2+ concentration at a range of stimulus frequencies. RESULTS: Resting cell length was significantly greater in the heart failure group; approximately 115% of control values in sub-epicardial and mid-myocardial cells, and approximately 108% in sub-endocardial cells. Using criteria described by previous studies on other mammalian hearts, functional M cells were identified by a higher maximum rate of depolarisation and longer action potential duration at 90% repolarisation (APD90) compared to the two other myocyte sub-types. In the heart failure group, APD90 and Ca2+ transient duration (CaD50) were prolonged in sub-epicardial and M cells but shortened in sub-endocardial myocytes. These changes were significant at lower stimulus frequencies, but the relative effect diminished at higher frequencies (3 Hz). Peak systolic [Ca2+] was reduced in sub-epicardial and M cells but increased in sub-endocardial cells in the heart failure group compared to controls. At higher stimulus frequencies, end diastolic Ca2+ levels were lower in sub-epicardial cells but higher in sub-endocardial myocytes of the heart failure group compared with controls. In general, changes were greater in heart failure animals with more severe in vivo ventricular dysfunction (ejection fraction < or = 44%). CONCLUSIONS: Heart failure was associated with an increased cell size throughout the left ventricle, but the form of the changes in electrophysiology and Ca2+ transient were dependent on the myocyte sub-type. In particular sub-endocardial cells displayed markedly different changes compared to the other myocyte sub-types.
Action Potentials↗
Effect of socioeconomic deprivation on waiting time for cardiac surgery: retrospective cohort study.
OBJECTIVE: To determine whether the priority given to patients referred for cardiac surgery is associated with socioeconomic status. DESIGN: Retrospective study with multivariate logistic regression analysis of the association between deprivation and classification of urgency with allowance for age, sex, and type of operation. Multivariate linear regression analysis was used to determine association between deprivation and waiting time within each category of urgency, with allowance for age, sex, and type of operation. SETTING: NHS waiting lists in Scotland. PARTICIPANTS: 26 642 patients waiting for cardiac surgery, 1 January 1986 to 31 December 1997. MAIN OUTCOME MEASURES: Deprivation as measured by Carstairs deprivation category. Time spent on NHS waiting list. RESULTS: Patients who were most deprived tended to be younger and were more likely to be female. Patients in deprivation categories 6 and 7 (most deprived) waited about three weeks longer for surgery than those in category 1 (mean difference 24 days, 95% confidence interval 15 to 32). Deprived patients had an odds ratio of 0.5 (0.46 to 0.61) for having their operations classified as urgent compared with the least deprived, after allowance for age, sex, and type of operation. When urgent and routine cases were considered separately, there was no significant difference in waiting times between the most and least deprived categories. CONCLUSIONS: Socioeconomically deprived patients are thought to be more likely to develop coronary heart disease but are less likely to be investigated and offered surgery once it has developed. Such patients may be further disadvantaged by having to wait longer for surgery because of being given lower priority.
Adolescent↗
Ventricular fibrillation threshold and local dispersion of refractoriness in isolated rabbit hearts with left ventricular dysfunction.
Patients with congestive heart failure or left ventricular dysfunction (LVD) have a high incidence of ventricular tachyarrhythmias and sudden cardiac death. In addition to structural, metabolic and neuroendocrine changes, mechanoelectrical feedback may play a role in arrhythmogenesis in heart failure. Three groups of rabbits (n = 10 for each) were studied: chronic coronary ligation with ejection fraction (EF) > or = 0.45 or < 0.45, and sham-operated controls. Ventricular fibrillation (VF) thresholds were measured at LV pressures of 0 and 40 mm Hg during modified Langendorff perfusion. Intervals between local activations during VF (VFI) were used as an index of refractoriness. Global dispersion was expressed as coefficient of variation of VFI; local dispersion by maximum difference in VFI between adjacent sites. Median VF threshold was lower at 0 mm Hg in the lower EF group compared to controls (30 vs. 67.5 mA, P<0.05). VF threshold in control hearts was lower at 40 mm Hg than at 0 mm Hg (P<0.01), but there was no further reduction in threshold in LVD hearts at 40 mm Hg. Global dispersion of VFI did not differ significantly between groups. Local dispersion of VFI in the lower EF group was greater than in controls at 0 mm Hg in the infarct border zone (P<0.05). At 40 mm Hg, local dispersion of VFI in zones bordering and remote from the infarct were greater in both LVD groups than in controls (P<0.05). Local inhomogeneity of refractoriness is more marked in the infarct border zone, but latent abnormalities are evident in normal myocardium of rabbits with left ventricular dysfunction and are revealed by left ventricular distension.
Animals↗
Regional electrophysiological effects of left ventricular hypertrophy in isolated rabbit hearts under normal and ischaemic conditions.
OBJECTIVES: Left ventricular hypertrophy (LVH) has been reported to produce differential electrophysiological effects in isolated epicardial and endocardial cells. This study aimed to examine regional electrophysiological effects of LVH in normal and ischaemic conditions in the whole heart. METHODS: LVH was secondary to perinephritis-induced hypertension. Monophasic action potential duration (MAPD(90)), effective refractory period (ERP) and conduction delay were measured in paced, isolated working rabbit hearts either at one right ventricular and two left ventricular sites (apical and basal epicardium) or at three left ventricular sites (apical and basal epicardium, apical endocardium). The hearts were subjected to 30 min of regional ischaemia and 15 min of reperfusion. RESULTS: In non-ischaemic conditions, LVH produced uniform prolongation of MAPD(90) and ERP in the left ventricular epicardium, but not in the endocardium. After coronary artery occlusion, LVH significantly increased ischaemia-induced transepicardial dispersion of repolarisation, but not refractoriness. LVH did not affect arrhythmogenesis in either non-ischaemic or ischaemic conditions. CONCLUSIONS: Differential effects of LVH on epicardial and endocardial electrophysiological parameters are also observed in the whole heart. In addition, the sensitivity of hypertrophied myocardium to ischaemia is increased and leads to an increase in ischaemia-induced dispersion of repolarisation. However, neither dispersion of refractoriness nor arrhythmogenesis are affected by LVH in non-ischaemic or ischaemic conditions in this experimental model.
Action Potentials↗
CPR '98: a practical multimedia computer-based guide to cardiopulmonary resuscitation for medical students.
This paper describes an initiative to build a multimedia computer-based teaching package for cardiopulmonary resuscitation. The project resulted from a perceived gap in the undergraduate medical curriculum allied to concern from medical students. The software application was designed to be networked and used as an adjunct to taught life support courses for undergraduate medical students. The package comprises tutorials and test questions in basic and advanced life support. It incorporates sound, video, graphics and animation to illustrate the techniques involved and is distributed on CD ROM for the PC. The content is based on the 'Advanced Life Support Manual', produced by the Resuscitation Council (UK) and incorporates all changes to the guidelines made during 1997 and 1998. The basic life support section has been networked locally, and has been tested on more than 60 third year medical students attending a local basic life support course. It was found that students who used the package performed significantly better in theoretical assessments than those who did not.
Cardiopulmonary Resuscitation↗
Sex differences in outcome following community-based cardiopulmonary arrest.
AIMS: To determine whether men and women suffering cardiopulmonary arrest differ in terms of survival and risk factors for survival. METHODS AND RESULTS: A prospective cohort study, using the Heartstart (Scotland) database, was undertaken on all 22 161 people suffering community-based cardiopulmonary arrest in Scotland between 1988 and 1997. The outcomes studied were death at the arrest scene, death before admission, death in hospital and death at any point up to discharge. Univariate analysis, using chi-square and Mann-Whitney U tests, was used to compare men and women in terms of patient characteristics, management and outcome. Multivariate logistic regression analysis was used to determine the association between sex and outcome after adjustment for case-mix. Sex differences in outcome varied over time. Women had a poorer risk profile than men. They were older (P<0.0001) and less likely to have shockable rhythms (P<0.0001). Despite this, they were more likely to survive to admission (P<0.0001). However, thereafter, women were more likely to die in hospital (P<0.01). There was no significant difference between the sexes in overall case-fatality rates to discharge. CONCLUSION: Women have a better early prognosis than men. However, this represents a postponement of death, rather than avoidance.
Aged↗
Congenital and acquired long QT syndrome.
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Action Potentials↗
Pressure damping, a "billowing" septum, and an eerie silence: perioperative, intermittent obstruction of a mitral valve prosthesis.
This case, involving a 74 year old man who underwent mitral valve and aortic valve replacements, provides detailed insight into the perioperative echocardiographic and haemodynamic changes occurring when a mitral valve prosthesis intermittently obstructs. It illustrates the early sequence of electromechanical dissociation which would lead to cardiac arrest should a tilting disc prosthesis be immobilised in the closed position.
Aged↗
The design of a prospective study of Pravastatin in the Elderly at Risk (PROSPER). PROSPER Study Group. PROspective Study of Pravastatin in the Elderly at Risk.
The PROspective Study of Pravastatin in the Elderly at Risk (PROSPER) is a randomized, double-blind, placebo-controlled trial designed to test the hypothesis that treatment with pravastatin will diminish risk of subsequent major vascular events in a cohort of men and women (70 to 82 years old) with preexisting vascular disease or significant risk of developing this condition. Five thousand eight hundred four men and women in addition to receiving advice on diet and smoking, have been randomized equally to treatment with 40 mg pravastatin/day or matching placebo in 3 centers (Cork, Ireland, Glasgow, Scotland, and Leiden, The Netherlands). Following an average 3.5-year intervention period, a primary assessment will be made of the influence of this therapy on major vascular events (a combination of coronary heart disease, death, nonfatal myocardial infarction, and fatal and nonfatal stroke). A number of additional analyses will also be conducted on the individual components of the primary end point, on men, on women, and on subjects with and without previous evidence of vascular disease. Finally, an assessment will be made of the effects of treatment on cognitive function, disability, hospitalization or institutionalization, vascular mortality, and all-cause mortality.
Aged↗
Facilitation of spontaneous defibrillation by moxonidine during regional ischaemia in an isolated working rabbit heart model.
Moxonidine has been shown to be antiarrhythmic during ischaemia in vivo. This study aimed to investigate its electrophysiological effects in isolated working rabbit hearts in vitro. Monophasic action potential duration, effective refractory period and conduction delay were measured at three ventricular sites. The hearts were treated before and during ischaemia and reperfusion with vehicle, moxonidine (0.01, 0.1 and 1 microM) or labetalol (1 microM). In all groups, ventricular fibrillation was always induced during ischaemia. Only 0.1 microM moxonidine decreased the incidence of sustained ventricular fibrillation from 86 to 17%, although it did not affect any electrophysiological parameters measured. Similarly, labetolol, an adrenoceptor blocker, facilitated spontaneous defibrillation without any electrophysiological effects. In conclusion, moxonidine directly facilitates spontaneous defibrillation of ventricular fibrillation during ischaemia. Since the same effect is observed with labetalol, it is possible that the defibrillatory action of moxonidine is related to its peripheral antiadrenergic activity, although other mechanisms cannot be excluded.
Action Potentials↗
Functional, structural, and dynamic basis of electrical heterogeneity in healthy and diseased cardiac muscle: implications for arrhythmogenesis and anti-arrhythmic drug therapy.
The electrophysiological properties of the ventricular myocardium are extremely heterogeneous. There are intrinsic electrical differences between the myocytes from different regions of the heart (most notably between the epicardium, midmyocardium, and endocardium), which are the result of different contributions of ionic currents to the transmembrane action potential. Sources of local anisotropy include directional differences in the distribution of gap junctions between adjacent myocytes and the presence of intercalated non-myocytes (e.g., fibroblasts), propagation boundaries, and wavefront collisions, which can lead to local variability of electrical load and, therefore, to nonuniform depolarisation and repolarisation. In addition, the complex anatomical arrangement of the myocardial fibres and nonuniform distribution of transmural mechanical stresses also contribute to electrical heterogeneity. Finally, dispersion of repolarisation is dynamically modified by the restitution properties of individual myocytes, stimulation rate, and the direction of conduction. All aspects of this electrical heterogeneity can be affected by different pathological conditions, such as myocardial ischaemia and cardiac hypertrophy. In particular, differential responses of various myocyte populations to these pathological stimuli and a marked increase in nonuniform anisotropy may be responsible for increased pro-arrhythmic potential in these conditions. In addition, the clinical effectiveness of anti-arrhythmic drugs may be related to their effects on electrical heterogeneity.
Action Potentials↗
Seasonal variations in coronary heart disease.
Coronary heart disease exhibits a winter peak and summer trough in incidence and mortality, in countries both north and south of the equator. In England and Wales, the winter peak accounts for an additional 20,000 deaths per annum. It is likely that this reflects seasonal variations in risk factors. Seasonal variations have been demonstrated in a number of lifestyle risk factors such a physical activity and diet. However, a number of studies have also suggested a direct effect of environmental temperature on physiological and rheological factors. We review the available evidence on seasonal variations in coronary heart disease and possible explanations for them.
Cold Climate↗
Relevance of inter- and intraventricular electrical dispersion to arrhythmogenesis in normal and ischaemic rabbit myocardium: a study with cromakalim, 5-hydroxydecanoate and glibenclamide.
This study aimed to investigate the role of electrical dispersion in arrhythmogenesis by using K(ATP) channel modulating agents. Monophasic action-potential duration (MAPD90), effective refractory period (ERP), and conduction delay were measured at three ventricular sites in isolated working rabbit hearts. Cromakalim (10 microM), glibenclamide (3 microM), or 5-hydroxydecanoate (100 microM) were administered before and throughout 30 min of regional ischaemia and 15 min of reperfusion. Before ischaemia, cromakalim reduced MAPD90 and ERP in all areas and facilitated induction of ventricular fibrillation in five of 12 hearts. In these hearts, cromakalim increased interventricular ERP dispersion from 17 +/- 5 to 38 +/- 5 ms. During ischaemia, cromakalim decreased MAPD90 dispersion within the left ventricle from 84 +/- 5 to 44 +/- 4 ms, but did not affect ERP dispersion and arrhythmogenesis. 5-Hydroxydecanoate had no effect on MAPD90 and ERP shortening or dispersion during ischaemia and reperfusion and was not antiarrhythmic. Glibenclamide reduced forward flow to zero, preventing further electrophysiologic studies. In conclusion, in this model, an increase in interventricular ERP dispersion predisposes to ventricular fibrillation in normoxic conditions after cromakalim administration. However, a decrease in ischaemia-induced MAPD90 dispersion by cromakalim does not affect arrhythmogenesis. A lack of effect of 5-hydroxydecanoate on electrical dispersion during ischaemia is accompanied by a lack of antiarrhythmic activity.
Action Potentials↗
Seasonal variations in out of hospital cardiopulmonary arrest.
OBJECTIVE: To determine whether there are seasonal variations in survival following out of hospital cardiopulmonary arrest. DESIGN: Prospective cohort study using the Heartstart (Scotland) database. SETTING: All of Scotland. PATIENTS: 10 890 people who suffered out of hospital cardiopulmonary arrest in the summer or winter between December 1988 and August 1997 inclusive. INTERVENTION: Univariate comparisons of 5406 arrests occurring in summer with 5484 in winter, in terms of patient characteristics, management, and survival using chi(2) and Mann-Whitney U tests. Multivariate analysis of the association between season and survival following adjustment for case mix. MAIN OUTCOMES MEASURES: Survival to discharge from hospital, survival pre-admission, in-hospital survival. RESULTS: Only 6% of people who arrested in winter survived to discharge, compared to 8% of those who arrested in summer (odds ratio 0.77, p < 0.001). People who arrested in winter had a poorer risk profile in that they were older, more likely to arrest at home, less likely to have a witness, and less likely to receive defibrillation. However, after adjustment for case mix, people who arrested in winter were still 19% less likely to survive compared to those who arrested in summer. Deaths pre-admission were significantly higher in winter (odds ratio 1.18, p < 0.05) but in-hospital deaths were not. CONCLUSIONS: People who suffer cardiopulmonary arrest in winter have a significantly lower likelihood of surviving. This is, in part, caused by the higher frequency of a number of recognised risk factors. However, their prognosis remains poorer even after adjustment for these factors.
Aged↗
Reduced sarcoplasmic reticulum Ca2+ release in rabbits with left ventricular dysfunction.
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Animals↗