Sympathetic nerve hyperactivity of essential hypertension is lower in postmenopausal women than men.

Sympathetic activation has been associated with the development and complications of hypertension. While the prevalence of hypertension and its cardiovascular risks in women are found to be less than in men and tend to become similar to men after the menopause, there have been no data on the level of sympathetic activation in postmenopausal women relative to men. Therefore, we planned to find out whether muscle sympathetic nerve hyperactivity of essential hypertension (EHT) in postmenopausal women is different from that in matched men. We quantified muscle sympathetic nerve activity (MSNA) as mean frequency of single units (s-MSNA) and multiunit bursts (b-MSNA) in 21 postmenopausal women with EHT (W-EHT) relative to 21 matched men with EHT (M-EHT), in comparison to two control groups of 21 normal women (W-NC) and 21 men (M-NC), respectively. The EHT groups had greater MSNA indices than NC groups. W-EHT had lower (P<0.05) s-MSNA (63+/-22.7 impulses per 100 cardiac beats) than M-EHT (78+/-11.2 impulses per 100 cardiac beats). W-NC had lower (P<0.05) s-MSNA (53+/-12.4 impulses per 100 cardiac beats) than M-NC (65+/-16.3 impulses per 100 cardiac beats). Similar results were obtained for b-MSNA. Postmenopausal women with EHT had lower level of central sympathetic hyperactivity than men. Similarly, normal postmenopausal women had lower MSNA than men. These findings suggest that postmenopausal women continue to have a lower sympathetic nerve activity than men even after the development of EHT, and that this could have implications for gender-specific management of hypertension.

The effect of gender on the sympathetic nerve hyperactivity of essential hypertension.

We planned to determine whether or not there is a difference in the level of muscle sympathetic nerve activity (MSNA) between hypertensive women and hypertensive men. Sympathetic activation of essential hypertension (EHT) has been associated with increased cardiovascular events, which are known to be less likely to occur in women than in men. Normal women have been reported to have less sympathetic nerve activity than men, but no reported data are available regarding gender differences in sympathetic activity in hypertensive subjects. We examined 36 patients with untreated and uncomplicated EHT comprising 18 women and 18 men, and 36 normal controls comprising 18 women and 18 men. MSNA was quantified as the mean frequency of single units and as multiunit bursts using the technique of microneurography. The hypertensive groups had greater sympathetic nerve activity than the control groups. Female hypertensives had lower (P<0.001) single unit hyperactivity (56+/-1.7 impulses/100 cardiac beats) than male hypertensives (72+/-1.7 impulses/100 cardiac beats). Normotensive females had lower (P<0.01) single unit activity (42+/-3.6 impulses/100 cardiac beats) than normotensive males (56+/-4.6 impulses/100 cardiac beats). Similar results were obtained for the frequency of multiunit burst activity. Hypertension in women is associated with a lower level of central sympathetic hyperactivity than in men. It is suggested that this may at least partly explain the observed lower hypertension-related cardiovascular events in women than in men. In addition, the findings may have implications for gender-specific management of hypertension.

Sympathetic nerve hyperactivity in non-diabetic offspring of patients with type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Type 2 diabetes mellitus with hyperinsulinaemia is a state of sympathetic nerve hyperactivity, which can develop subsequently in non-diabetic first-degree offspring of patients with type 2 diabetes. Although both type 2 diabetes and sympathetic activation are major cardiovascular risk factors, the level of sympathetic nerve activity is as yet unknown in offspring of type 2 diabetic patients who are ostensibly normal. We therefore sought to quantify sympathetic nerve activity and its relationship to plasma insulin levels in ostensibly normal offspring of patients with type 2 diabetes, relative to a matched normal control group with no family history of type 2 diabetes. SUBJECTS AND METHODS: In two closely matched groups comprising 23 non-diabetic offspring of type 2 diabetic patients and 23 normal control individuals we measured resting muscle sympathetic nerve activity (MSNA) as the mean frequency of multi-unit bursts of MSNA and single units of MSNA (s-MSNA) with defined vasoconstrictor properties. RESULTS: In offspring of type 2 diabetic patients, the fasting plasma levels of insulin (7.4+/-0.80 microU/ml) and s-MSNA (45+/-3.2 impulses/100 beats) were greater (p<0.009 and p<0.003) than those in control persons (4.6+/-0.76 microU/ml and 32+/-3.1 impulses/100 beats, respectively). MSNA bursts and derived insulin resistance followed similar trends. Sympathetic nerve activity was significantly correlated to insulin levels (p<0.0002) and resistance (p<0.0001) in offspring of type 2 diabetic patients, but not in control subjects. CONCLUSIONS/INTERPRETATION: Sympathetic activation occurred in normal non-diabetic offspring of patients with type 2 diabetes in proportion to their plasma insulin levels. Our data indicate the presence of a mechanistic link between hyperinsulinaemia and sympathetic activation, both of which could play a role in the subsequent development of cardiovascular risk factors.

Disparity of autonomic control in type 2 diabetes mellitus.

AIMS/HYPOTHESIS: Acute insulinaemia activates the sympathetic drive in a nonuniform manner. The extent and nature of such activation in type 2 diabetic patients who do not have neuropathy have not yet been addressed despite evidence relating sympathetic activation to cardiovascular risk. We planned to determine the magnitude and extent of the sympathetic drive and its reflex responses in patients with type 2 diabetes and fasting hyperinsulinaemia. METHODS: We measured resting muscle sympathetic nerve activity (MSNA) as the mean frequency of multi-unit bursts and single unit muscle sympathetic nerve activity (s-MSNA) in 17 overweight patients with type 2 diabetes and two matched normal control groups comprising 17 overweight and 16 normal-weight subjects. We also tested the MSNA and s-MSNA responses to cold pressor and isometric hand-grip tests, along with the effect of sympatho-vagal balance on heart period variability. RESULTS: Both MSNA and s-MSNA in the group with type 2 diabetes (66+/-3.5 bursts/100 beats and 78+/-4.5 impulses/100 beats) were greater (at least p<0.0001) than in the overweight control group (42+/-2.6 bursts/100 beats and 48+/-3.4 impulses/100 beats) and normal-weight control group (43+/-6.2 bursts/100 beats and 51+/-7.1 impulses/100 beats), though the three groups had similar reflex responses, baroreflex sensitivity and sympatho-vagal balance controlling the heart period. CONCLUSIONS/INTERPRETATION: The patients with type 2 diabetes had no evidence of impaired reflex or autonomic control of heart period variability at a time when there was central sympathetic activation to the periphery. Furthermore, being overweight itself was not associated with sympathetic activation.

Does balloon mitral valvuloplasty improve cardiac function? A mechanistic investigation into impact on exercise capacity.

Procedural technical success of balloon mitral valvuloplasty (BMV) is indicated by an increase in valve area and a reduction in transvalvar gradient, but there are conflicting results regarding whether these indicators correlate with subsequent improvements in exercise capacity. We conducted a study to explore the effects of valvuloplasty on cardiac function to gain insight into the mechanisms responsible for the impact on exercise ability. Sixteen patients with mitral stenosis participated in the study and the five who did not proceed to valvuloplasty served as the control group. All patients performed maximal cardiopulmonary exercise tests before and 6 weeks after valvuloplasty (without valvuloplasty in controls). Central haemodynamics including cardiac output were measured non-invasively at rest and peak exercise. At baseline, the cardiopulmonary exercise test results were similar in the two groups. Following valvuloplasty, cardiac output did not alter at rest, but increased significantly at peak exercise (8.7+/-1.7 to 10.5+/-2.1 l min(-1), P<0.01), as did peak cardiac power output (1.88+/-0.55 to 2.28+/-0.74, P<0.05) and cardiac reserve (1.07+/-0.33 to 1.45+/-0.55 watts, P<0.05). Aerobic exercise capacity improved (13.9+/-4.2 to 16.4+/-4.3 ml kg(-1) min(-1), P<0.01) as did exercise duration (354+/-270 to 500+/-266 s, P<0.01). There were no significant changes in the controls. There was a significant correlation between the changes in peak VO(2) and changes in cardiac reserve (r=0.62, P<0.01) but not with changes in resting haemodynamics. These changes did not correlate with changes in peri-procedural mitral valve haemodynamics, despite increases in mitral valve area from 1.05+/-0.16 to 1.74+/-0.4 cm(2) (P<0.0001), accompanied by falls in the transvalvar gradient and pulmonary artery pressure (12.4+/-4.7 to 4.5+/-3 mmHg, and 26.8+/-8.4 to 17.4+/-5.2 mmHg, respectively, all P<0.0001). In conclusion, we found that successful mitral valvuloplasty in our patient cohort led to improved cardiac and physical functional capacity but not resting haemodynamics. Neither indicators of technical success nor resting haemodynamics were very reliable in predicting functional improvement.

Troponin for acute coronary syndromes: has NICE got it right?

The guidelines on the use of glycoprotein IIb/IIIa inhibitors for acute coronary syndromes issued by the National Institute for Clinical Excellence (NICE) recommend that blood troponin is used to identify patients who might benefit from therapy. There are, however, a number of circumstances in which troponin results may be misleading. Firstly, the trials which comprise the evidence base for the therapeutic effect were only based on patients with documented coronary artery disease. Secondly, troponin is elevated in patients with heart failure and concentrations fall with appropriate treatment. Thirdly, there is no internationally accepted standard for troponin, and there are therefore important differences at the 'cut-off' values between the methods of different manufacturers. Fourthly, immunoassays suffer from interfering antibodies and at least 17 case reports have been published outlining false positive tests. It is important that the shortfalls of troponin tests in the diagnosis of acute coronary syndromes are widely recognized.

Use of cumulative mortality data in patients with acute myocardial infarction for early detection of variation in clinical practice: observational study.

OBJECTIVES: Use of cumulative mortality adjusted for case mix in patients with acute myocardial infarction for early detection of variation in clinical practice. DESIGN: Observational study. SETTING: 20 hospitals across the former Yorkshire region. PARTICIPANTS: All 2153 consecutive patients with confirmed acute myocardial infarction identified during three months. MAIN OUTCOME MEASURES: Variable life-adjusted displays showing cumulative differences between observed and expected mortality of patients; expected mortality calculated from risk model based on admission characteristics of age, heart rate, and systolic blood pressure. RESULTS: The performance of two individual hospitals over three months was examined as an example. One, the smallest district hospital in the region, had a series of 30 consecutive patients but had five more deaths than predicted. The variable life-adjusted display showed minimal variation from that predicted for the first 15 patients followed by a run of unexpectedly high mortality. The second example was the main tertiary referral centre for the region, which admitted 188 consecutive patients. The display showed a period of apparently poor performance followed by substantial improvement, where the plot rose steadily from a cumulative net lives saved of -4 to 7. These variations in patient outcome are unlikely to have been revealed during conventional audit practice. CONCLUSIONS: Variable life-adjusted display has been integrated into surgical care as a graphical display of risk-adjusted survival for individual surgeons or centres. In combination with a simple risk model, it may have a role in monitoring performance and outcome in patients with acute myocardial infarction.

Antiarrhythmic management and implantable defibrillator use in survivors of prehospital cardiac arrest without myocardial infarction in West Yorkshire.

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.

Management and health status in the first year after out-of-hospital cardiac arrest.

The one-year survival, functional and cerebral capacity and patient management following out-of-hospital cardiac arrest were examined in a follow-up study of 143 prospectively identified patients discharged from a West Yorkshire hospital between January 1987 and July 1993. One-year survival was 87%; 13 of the 18 deaths were cardiac related; 89% of survivors had no further cardiac related admissions; 98% of patients surviving to one year were capable of independent daily activities. There was low utilisation of simple drug therapy: 23% of patients were discharged taking beta-blockers and 52% aspirin; 50% of patients discharged after a primary arrhythmic event were taking antiarrhythmic therapy or were given an implantable defibrillator. Irrespective of the availability of invasive cardiac facilities, there was underutilisation of investigations: only 39% of patients were seen by a cardiologist and 54% were not evaluated for ischaemic risk. Significant improvements in patient management could probably be achieved quickly without substantial increases in resources.

Late, intermittent obstruction of a mitral prosthesis by chordal remnants.

A 59 year old male was admitted 10 weeks following insertion of a Medtronic Hall mitral prosthesis. He suffered recurrent episodes of electromechanical dissociation (EMD). Transthoracic echocardiography demonstrated that during the times of haemodynamic compromise, the mitral prosthesis was intermittently obstructed. Emergency surgical intervention revealed that chordae tendineae had prolapsed through the lesser orifice, obstructing the valve mechanism. The mitral remnants were excised, and as the valve functioned normally, it was not replaced. Postoperatively, the patient made an uneventful recovery. This case illustrates the Doppler echocardiographic features associated with extrinsic obstruction of a mitral prosthesis, and demonstrates that this unusual complication can be responsible for late valve dysfunction.

Automatic recording and timing of defibrillation on general wards by day and night.

To measure the speed of response to ventricular fibrillation on general medical wards and to assess the importance of this and other factors for survival to leave hospital, 69 consecutive patients with ventricular fibrillation were studied prospectively using an automatic timing device in the hospital telephone exchange and an automatic timer and ECG recording during resuscitation. Twenty-seven patients were initially resuscitated and 17 were discharged from hospital. The median time to connect the monitor after recognition of a cardiac arrest was 127 s (range 0-277) for survivors and 132.5 s (range 0-620) for non-survivors. The median time ventricular fibrillation was displayed before the first shock was 43 s (range 4-75) for survivors and 52 s (range 10-454) for non-survivors. These differences were not significant; but logistic regression analysis identified primary ventricular fibrillation, short display time (logged data), 'early' time of day, absence of pre-existing non-cardiac illness, and post-defibrillation heart-rate > 30 beats.min-1 in rank order as independent predictors of survival. In spite of no significant diurnal variation in response time, successful resuscitations were concentrated in the early nursing shift (0730-1530 h). Four shocks were inappropriate. Clinical diagnosis was more predictive of outcome than the time to the first shock. The reasons for the poorer results in the evening and night are uncertain.

Comparison of two methods of transporting paramedics to cardiac arrests outside hospital.

OBJECTIVE: To compare the deployment of paramedics in a separate rapid response unit with their deployment in a standard emergency ambulance. DESIGN: A one year period of each deployment. SETTING: Throughout the community in some parts of West Yorkshire. PARTICIPANTS: All patients receiving resuscitation for cardiac arrest by paramedics. INTERVENTIONS: Using the same group of paramedics and central control, 12 months with the paramedics deployed in separate cars in addition to the standard ambulances (period 1) were followed by another 12 months when they were deployed as one crew member of a standard emergency ambulance (period 2). MAIN OUTCOME MEASURES: Number of arrests attended, number of patients in ventricular fibrillation at paramedic arrival, response times, survival to leave hospital. RESULTS: In period 1, 580 arrests were attended with 31 survivors. In period 2, 462 arrests resulted in 25 survivors. The mean response time was shorter in period 1 (6.24 versus 6.60 min, Cl--0.01-0.73 min). In period 1, 217 patients were found in ventricular fibrillation (23 survivors): In period 2, 141 patients were found in ventricular fibrillation (11 survivors). CONCLUSION: Separating paramedics from the standard emergency ambulances increases the number of survivors of cardiac arrest but the difference may not be sufficiently large to justify the additional expenditure.

The Acute Infarction Ramipril Efficacy (AIRE) Study: rationale, design, organization, and outcome definitions.

The rationale, design, organization, and outcome definitions of the Acute Infarction Ramipril Efficacy (AIRE) Study are described prospectively. A total of 2,000 patients (1,000 per treatment group) will be recruited to this multicenter, multinational, double-blind, randomized, placebo-controlled study investigating the effect of oral treatment with ramipril (2.5 or 5 mg twice daily) on the total mortality of survivors of an acute myocardial infarction (AMI) with early clinical evidence of heart failure. Secondary outcomes of the study include progression to severe/resistant heart failure (at which time the patient will be withdrawn from the study treatment), reinfarction, and stroke. Treatment will be initiated in hospital between day 3 and day 10 following AMI, and follow-up continued for an average of 15 months and a minimum of 6 months. The study data will be analyzed on an intention-to-treat basis: a single formal interim analysis will be conducted after 175 deaths. An Independent Adjudicating Panel will act as the overall ethical supervisory body for the study and will retain the randomization code. An International Steering Committee will be responsible for the clinical definitions of the secondary study outcomes, and will regularly review progress of the study. We believe that early treatment with ramipril may reduce the total mortality of patients surviving an AMI with clinical evidence of heart failure.

Resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire.

OBJECTIVE: To investigate the results of resuscitation of patients with cardiac arrest by ambulance staff with extended training in West Yorkshire. DESIGN: Study of all such attempts at resuscitation over 32 months, based on the standard report form for each call made by the ambulance staff and the electrocardiogram that showed the initial rhythm in each patient. SETTING: Area covered by West Yorkshire ambulance service. SUBJECTS: 1196 Patients with cardiac arrests attended by 29 ambulance staff with extended training. MAIN OUTCOME MEASURE: Result of resuscitation. RESULTS: The initial rhythm was asystole or electromechanical dissociation in 740 patients and ventricular fibrillation in 456 patients; overall 65 patients survived to be discharged from hospital. Sixty four of the 456 patients in whom ventricular fibrillation was the initial rhythm recorded, and 46 in whom ventricular fibrillation persisted after the ambulance staff arrived, survived. Only one of the 740 patients who initially had asystole or electromechanical dissociation survived. Factors associated with a greater chance of ventricular fibrillation occurring were: age less than 71, the arrest being witnessed by a bystander, resuscitation by a bystander, the arrest occurring in a public place, and a response time by the ambulance staff of less than six minutes. For patients found in ventricular fibrillation a shorter response time was associated with improved survival but resuscitation by a bystander was not. Additional skills learnt during extended training were used for 51 of the 65 patients who survived. CONCLUSIONS: Ambulance staff with extended training can save the lives of patients with cardiac arrest due to fibrillation, though asystole and electromechanical dissociation have a poor prognosis and should perhaps receive little attention during extended training.

QT sensing rate responsive pacing during subacute bacterial endocarditis: a case report.

A 63-year-old woman treated with a QT sensing rate responsive pacemaker following aortic valve replacement developed late subacute bacterial endocarditis. During febrile periods, associated with systemic upset, pacing was physiological as evidenced by an increased heart rate during pyrexia and a decrease when afebrile.

Combined percutaneous balloon dilatation of the aortic valve and coronary angioplasty.

A 75 year old man with severe angina caused by aortic stenosis and coronary artery disease was considered to be unsuitable for cardiac surgery after the recent removal of a bronchial carcinoma. Combined percutaneous balloon dilatation of the aortic valve and right coronary angioplasty considerably ameliorated the patient's angina.

Oral xamoterol in patients with sinoatrial disease.

Twelve patients with sinoatrial disease were assessed while on oral xamoterol (200 mg twice daily) and placebo by a double blind randomised, crossover trial that lasted four weeks. Nine of the patients had been referred for permanent pacing. Xamoterol produced favourable changes in the number of pauses and the mean heart rate in six patients. Another patient deteriorated on xamoterol. Six patients were started on long term xamoterol. Xamoterol produces short term electrocardiographic improvement in some, but not all, patients with symptomatic sinoatrial disease.

Accessory atrioventricular pathway in association with ventricular septal aneurysm.

An unusual combination of ventricular pre-excitation, right ventricular dysplasia and a ventricular septal aneurysm is described in a 23-year-old woman. The presence of an accessory pathway was confirmed. The potential embryological mechanisms are discussed.