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Context: Population-based screening has been advocated for subclinical thyroid dysfunction in the elderly because the disorder is perceived to be common, and health benefits may be accrued by detection and treatment. Objective: The objective of the study was to determine the prevalence of subclinical thyroid dysfunction and unidentified overt thyroid dysfunction in an elderly population. Design, Setting, and Participants: A cross-sectional survey of a community sample of participants aged 65 yr and older registered with 20 family practices in the United Kingdom. Exclusions: Exclusions included current therapy for thyroid disease, thyroid surgery, or treatment within 12 months. Outcome Measure: Tests of thyroid function (TSH concentration and free T 4 concentration in all, with measurement of free T3 in those with low TSH) were conducted. Explanatory Variables: These included all current medical diagnoses and drug therapies, age, gender, and socioeconomic deprivation (Index of Multiple Deprivation, 2004) Analysis: Standardized prevalence rates were analyzed. Logistic regression modeling was used to determine factors associated with the presence of subclinical thyroid dysfunction Results: A total of 5960 attended for screening. Using biochemical definitions, 94.2% [95% confidence interval (CI) 93.8-94.6%] were euthyroid. Unidentified overt hyper- and hypothyroidism were uncommon (0.3, 0.4%, respectively). Subclinical hyperthyroidism and hypothyroidism were identified with similar frequency (2.1%, 95% CI 1.8-2.3%; 2.9%, 95% CI 2.6-3.1%, respectively). Subclinical thyroid dysfunction was more common in females (P < 0.001) and with increasing age (P < 0.001). After allowing for comorbidities, concurrent drug therapies, age, and gender, an association between subclinical hyperthyroidism and a composite measure of socioeconomic deprivation remained. Conclusions: Undiagnosed overt thyroid dysfunction is uncommon. The prevalence of subclinical thyroid dysfunction is 5%. We have, for the first time, identified an independent association between the prevalence of subclinical thyroid dysfunction and deprivation that cannot be explained solely by the greater burden of chronic disease and/or consequent drug therapies in the deprived population. Copyright © 2006 by The Endocrine Society.

Background A 75-year-old man had a myocardial infarction complicated by poor left ventricular function and non-sustained ventricular tachycardia. He began treatment with amiodarone and 12 months later developed symptoms of thyrotoxicosis. Investigations Thyroid function tests after commencement of amiodarone revealed a high-normal level of free T4 and low-normal level of free T3 with a normal serum TSH. When symptoms of thyrotoxicosis developed, significant rises in T4 and T3 levels and suppression of TSH were observed. Thyroid autoantibodies were detected and thyroid ultrasonography revealed a small multinodular goiter. Diagnosis Amiodarone-induced thyrotoxicosis (AIT) with features consistent with both AIT type I (in which thyroid antibodies and nodular goiter are present) and AIT type II (which is not responsive to thionamide therapy and eventually leads to permanent hypothyroidism). Management The patient continued to be treated with amiodarone. He commenced thionamide (carbimazole) therapy but failed to improve, even after a dose increase. Glucocorticoid (prednisolone) therapy was therefore added. Combination therapy was associated with gradual clinical and biochemical improvement. The patient became persistently hypothyroid after stopping thionamide and glucocorticoid therapy and was stabilized on long-term thyroxine replacement.

Objectives This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy. Background Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality. Methods A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm. Results A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months. Conclusions Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy.

Recent work has shown no difference in change of LVEF between RV apical (RVA) pacing and non-RVA pacing in patients with normal LV function. We hypothesised that a more sensitive marker (global longitudinal strain, GLS) could identify a detrimental effect of RVA and that assessment of deformation could identify whether dyssynchrony, contraction inefficiency and regional LV impairment were responsible for functional changes.In this substudy of Protect-PACE (The Protection of Left Ventricular Function During Right Ventricular Pacing. Does Right Ventricular High-septal Pacing Improve Outcome Compared With Right Ventricular Apical Pacing?), a randomised controlled trial of RVA and non-RVA pacing in pacemaker-dependent patients with preserved EF, 145 patients (76 with RVA) with echocardiograms of sufficient quality underwent measurement of LV longitudinal strain (GLS) from speckle tracking just after implantation and at 2 years. LV dyssynchrony, discoordination and regional apical longitudinal strain were also measured.Pacing was associated with reduced GLS after 2 years, although 2-year GLS was lower in RVA (-13.9 ± 4.1 vs -15.5 ± 4.6, p = 0.02). RVA was an independent correlate of ΔGLS, although there was a minor difference in ΔGLS between the RVA and non-RVA groups (-1.8 ± 3.6 vs -0.8 ± 3.4%, p= 0.07), reflecting impairment of GLS at baseline in RVA. Apical strain was significantly lower in RVA than those in non-RVA at baseline and 2 years (both p0.01). Dyssynchrony and discoordination parameters at 2 years also showed significant deterioration in RVA. Apical strain, dyssynchrony and discoordination parameters at 2 years were significantly associated with ΔGLS.Inefficient dyssynchronous contraction and the decrease in apical strain appear to be associated with global LV impairment in RVA.PROTECT-PACE ClinicalTrials.gov number NCT00461734.

Background and Objectives Routine statistics and epidemiologic studies often distinguish between types of cardiac death. Our aim was to assess agreement between doctors on cause of death given identical clinical information, and to assess agreement between a physician panel and the original cause of death as coded on national statistics. Methods Clinical information and autopsy reports on 400 cardiac deaths were randomly selected from a defined population in the West Midlands, UK. A panel of eight clinicians was assembled, and batches of 24–25 cases were sent to pairs of these clinicians who, blinded to the certified cause of death, independently of each other assigned underlying cause of death. Physician panel decision was achieved by consensus. Levels of agreement were assessed using the kappa statistic. Results Reviewers agreed on cause of death in 54% of cases (kappa = 0.34). Consensus decision of reviewers agreed with death certificate diagnosis in 61.5% (kappa = 0.39). Agreement was higher if an autopsy had been performed (kappa = 0.49). Conclusion The process of identifying underlying cause of death is of limited reliability, and therefore, limited accuracy. This has implications for design of epidemiologic studies and clinical trials of cardiovascular disease.

Purpose: Reduced lead diameter and reliability can be designed into transvenous permanent pacing leads through use of redundant insulation and removal of the stylet lumen. The model 3830 lead (Medtronic Inc., Minneapolis, MN, USA) is a bipolar, fixed-screw, steroid-eluting, lumenless, 4.1-Fr pacing lead. Implantation can be performed in a variety of right heart sites using a deflectable catheter (Model 10600, Medtronic). Lead performance and safety were studied. Methods: Two prospective trials of 338 implanted subjects from 56 global sites were conducted. Electrical and safety data were obtained at implant, pre-discharge, and up to 18 months post-implant. Leads were implanted at traditional and alternate right heart sites. Results: The study enrolled 338 subjects (204 males, 70.6 ± 11.6 years) followed-up for a mean of 10.2 months (range, 0–21.6). Mean P-wave amplitudes ranged from 3.2 mV at 3 months to 2.9 mV at 18 months, while mean atrial pulse width thresholds at 2.5 V ranged from 0.07 ms at 3 months to 0.09 ms at 18 months. Mean R-wave amplitudes ranged from 11.3 mV to 11.1 mV and mean ventricular pulse width thresholds at 2.5 V ranged from 0.10 ms to 0.14 ms. There were 22 ventricular and 12 atrial lead complications within 3 months post-implant. Survival from lead-related complications improved to a clinically acceptable rate in the cohort of patients when revised implant techniques were employed. Conclusions: With the use of recommended implant techniques, the study results support the electrical efficacy and safety of a catheter-delivered, lumenless lead in traditional or alternate right atrium or right ventricle sites through 18 months post-implant.

Patients with subclinical and treated overt hyperthyroidism have an excess vascular mortality rate. Several symptoms and signs in overt hyperthyroidism suggest abnormality of cardiac autonomic function that may account in part for this excess mortality rate, but few studies have examined cardiac autonomic function in untreated and treated hyperthyroidism. We assessed heart rate turbulence (HRT) and time-domain parameters of heart rate variability in a large, unselected cohort of patients with overt hyperthyroidism referred to our thyroid clinic (n = 259) and compared findings with a group of normal subjects with euthyroidism (n = 440). These measures were also evaluated during antithyroid therapy (when serum-free thyroxine and triiodothyronine concentrations returned to normal but thyrotropin remained suppressed (i.e., subclinical hyperthyroidism, n = 110) and when subjects were rendered clinically and biochemically euthyroid (normal serum thyrotropin, free thyroxine and triiodothyronine concentrations, n = 219). We found that overall measures of heart rate variability and those specific for cardiac vagal modulation were attenuated in patients with overt hyperthyroidism compared with normal subjects; measurements of overall heart rate variability remained low in those with low levels of serum thyrotropin but returned to normal in patients with biochemical euthyroidism. Measurements of HRT (onset and slope) were also decreased in patients with overt hyperthyroidism, but HRT slope returned to normal values with antithyroid treatment. This study is the first to evaluate HRT in overt and treated hyperthyroidism.

Selective site right ventricular pacing has been suggested as an approach to reduce the incidence of ventricular dysfunction and hopefully influence the morbidity resulting from traditional right ventricular apical pacing. Pacing from the right ventricular apex allows a stable ventricular rate, and together with atrial pacing and sensing, helps maintain atrioventricular synchrony but does not allow physiological activation of the left ventricle. Traditional atrial pacing sites like the right atrial appendage may encourage atrial tachyarrhythmias, whereas lead placement in right atrial septal sites may reduce the frequency of symptomatic atrial tachyarrhythmia episodes, especially when combined with prevention algorithms. Researchers attempting to pace the heart from these selective sites have been hindered by the lack of uniform definitions of where these sites actually lie and the inadequacy of tools to consistently reach these locations and verify correct placement. This lack of definition consensus may have contributed to the apparent conflict of data, particularly in the right ventricle. There is an urgent need for a standardization of terms and identifying measures for selective pacing sites.

Clinical evidence is accumulating that pacing from traditional right-sided sites (right ventricular apex and right atrial appendage) may be associated with long-term detriment to left ventricular function and promotion of atrial arrhythmias. Large numbers of small studies, some randomized, have addressed the effects of pacing from nontraditional or alternate sites, but the studies have varied in design such that comparison of results is often difficult. Many studies show data from acute studies only, although more recently longer-term data have started to become available; definition and description of pacing site also varies, adding further to the difficulties in comparing data. This article attempts to examine the randomized studies available to date, and to consider how future studies may contribute to our understanding of the effects of pacing from traditional and selected, specific sites on the right side of the heart.

Objectives We tested the hypothesis that left ventricular (LV) pacing is superior to right ventricular (RV) apical pacing in patients undergoing atrioventricular (AV) junction ablation and pacing for permanent atrial fibrillation. Background The potential benefit of LV over RV pacing needs to be evaluated without the confounding effect of other variables that can influence cardiac performance. Methods An acute intrapatient comparison of the QRS width and echocardiographic parameters between RV versus LV pacing was performed within 24 h after ablation in 44 patients. Both modes of pacing were also compared with pre-implantation values. Results Compared with RV pacing, LV pacing caused a 5.7% increase in the ejection fraction (EF) and a 16.7% decrease in the mitral regurgitation (MR) score; the QRS width was 4.8% shorter with LV pacing. Similar results were observed in patients with or without systolic dysfunction and/or native left bundle branch block, except for a greater improvement in MR in the latter group. Compared with pre-ablation measures, the EF increased by 11.2% and 17.6% with RV and LV pacing, respectively; the MR score decreased by 0% and 16.7%; and the diastolic filling time increased by 12.7% and 15.6%. Conclusions Rhythm regularization achieved with AV junction ablation improved EF with both RV and LV pacing; LV pacing provided an additional modest but favorable hemodynamic effect, as reflected by a further increase of EF and reduction of MR. The effect seems to be equal in patients with both depressed and preserved systolic functions and in those with and without native left bundle branch block.

Hyperthyroidism is a common disorder affecting multiple systems in the body. The cardiovascular effects are among the most striking. The availability of effective treatments for hyperthyroidism has led to the widespread perception that it is a reversible disorder without any long-term consequences. Recent evidence suggests, however, that there may be adverse outcomes. Long-term follow-up studies have revealed increased mortality from cardiovascular and cerebrovascular disease in those with a past history of overt hyperthyroidism treated with radioiodine, as well as those with subclinical hyperthyroidism. Thyroid hormones are known to exert direct effects on the myocardium, as well as the systemic vasculature and predispose to dysrhythmias, especially supraventricular. Atrial fibrillation (AF) is a recognized complication of overt hyperthyroidism, and subclinical hyperthyroidism is also known to be a risk factor for development of AF. Supraventricular dysrhythmias, particularly atrial fibrillation, in older patients may account for some of the excess cardiovascular and cerebrovascular mortality described, especially because AF is known to predispose to embolic phenomena.

Thyrotoxicosis is often perceived as a reversible disorder without long-term consequences, perhaps because of the availability of effective treatments, but recent evidence suggests that there may, in fact, be adverse outcomes. Long-term follow-up studies have revealed increased mortality from cardiovascular and cerebrovascular disease in those with a past history of overt hyperthyroidism treated with radioiodine as well as in those with subclinical hyperthyroidism indicated by a low serum TSH concentration. Thyroid hormones exert direct effects on the myocardium as well as the systemic vasculature predisposing to dysrhythmias, especially supraventricular. Effects of thyroid hormones on the autonomic nervous system may also contribute to arrhythmogenesis. Atrial fibrillation is a recognized complication of hyperthyroidism that predisposes to embolic events. Development of atrial fibrillation, together with other supraventricular dysrhythmias (both clinically obvious and those detected only by Holter monitoring) in those with hyperthyroidism may account for increased vascular mortality. Improved detection of supraventricular dysrhythmias and therapeutic intervention (e.g. anticoagulants, antiarrhythmics) may improve the long-term vascular prognosis, but their role remains to be established in large therapeutic trials.

Infections related to implantable cardiac electronic devices (ICEDs), including pacemakers, implantable cardiac defibrillators and cardiac resynchronization therapy devices, are increasing in incidence in the USA and are likely to increase in the UK, because more devices are being implanted. These devices have both intravascular and extravascular components and infection can involve the generator, device leads and native cardiac structures or various combinations. ICED infections can be life-threatening, particularly when associated with endocardial infection, and all-cause mortality of up to 35% has been reported. Like infective endocarditis, ICED infections can be difficult to diagnose and manage. This guideline aims to (i) improve the quality of care provided to patients with ICEDs, (ii) provide an educational resource for all relevant healthcare professionals, (iii) encourage a multidisciplinary approach to ICED infection management, (iv) promote a standardized approach to the diagnosis, management, surveillance and prevention of ICED infection through pragmatic evidence-rated recommendations, and (v) advise on future research projects/audit. The guideline is intended to assist in the clinical care of patients with suspected or confirmed ICED infection in the UK, to inform local infection prevention and treatment policies and guidelines and to be used in the development of educational and training material by the relevant professional societies. The questions covered by the guideline are presented at the beginning of each section.

Thyroid hormones exert important effects on the cardiovascular system, including effects on cardiac systolic and diastolic function, peripheral vascular resistance and arrhythmogenesis. Hyperthyroidism and hypothyroidism often cause opposing effects on cardiovascular physiology in the short term. Increasing evidence suggests that long-term vascular morbidity and mortality occurs in both overt and subclinical thyroid disease.

Paul Zoll first applied clinically effective temporary cardiac pacing in 1952 using a pulsating current applied through two electrodes attached via hypodermic needles to the chest wall in two patients with ventricular standstill.1 Although this technique was uncomfortable for the patients it was effective for 25 minutes in one patient and nearly five days in the second; this report heralded the ability to provide temporary ventricular rate support for patients with clinically significant bradycardia. Subsequent technological developments have provided endocardial, epicardial, and gastrooesophageal approaches to temporary cardiac pacing in addition to the refinement of external pacing. All approaches, however, are based on the provision of rate support from an external pulse generator via an electrode or electrodes which can be removed easily after a short period of pacing, as many of the situations requiring temporary pacing are transient and resolve spontaneously or have a correctable underlying cause. In a selected group of patients, permanent pacing treatment will need to be instigated before removal of the temporary system. The indications for temporary pacing can be considered in two broad categories: emergency (usually associated with acute myocardial infarction) or elective. There is, however, no clear consensus on indications for temporary pacing with most recommendations coming from clinical experience rather than scientific trials.2 For many patients presenting with bradycardia, however, conservative therapy and treatment of the underlying problem is the most appropriate management strategy. As a general rule, patients who may need to go on to permanent pacing should only have a temporary transvenous pacing wire placed if they have suffered syncope at rest, are haemodynamically compromised by the bradycardia or have ventricular tachyarrhythmias in response to bradycardia. In particular, patients presenting with sinus node disease rarely need temporary pacing, and the risks of infection and compromise of subsequent venous access …

Atrioventricular junctional (AVJ) catheter ablation followed by pacemaker implantation is now widely accepted for patients affected by paroxysmal atrial fibrillation (PAF) not controlled by antiarrhythmic drugs. However, few data exist on its indications, optimal methodology and complications. Therefore a study group examined current practice in Europe and North America, using a questionnaire, followed by a Study Group Meeting to discuss the results. Based upon this, class I, class II and class III indications were proposed. Class I indications (for which general agreement existed) include drug-refractory PAF, correlating with important symptoms, the bradycardia–tachycardia syndrome already treated with a pacemaker, and continued PAF. Large differences exist in the current methodology, but consensus was reached on the technical approaches of right and left-sided AVJ ablation, and on the timing of pacemaker implant in relation to ablation. No complete agreement was reached on technical features such as catheter choice and heparin use. The recommended pacing mode was DDDR with mode switching.

Aims Various mode-switching algorithms are available with different tachyarrhythmia detection criteria to be satisfied to initiate mode-switching. This study evaluated three different mode-switching algorithms in patients with paroxysmal atrial fibrillation. Methods and Results Seventeen patients completed the study. Three mode-switching algorithms were downloaded as software into the pacemaker, each for 1 month in a single-blind, randomized sequence. The criteria to initiate mode-switching were: mean atrial rate (‘standard’), ‘4-of-7’ or ‘1-of-1’ atrial intervals to exceed the atrial detection rate. Symptoms for each were measured using the Symptom Checklist–Frequency and Severity index. The median number of mode-switch episodes increased from 20 for ‘standard’ to 39 for ‘4-of-7’ (P=0·029 vs ‘standard’) and 103 for ‘1-of-1’ (P=0·0012 vs ‘standard’) onset criteria. Median duration of episodes decreased from 2·5 min with ‘standard’ to 1·4 min with ‘4-of-7’ and 0·4 min with ‘1-of-1’ onset criteria. Frequency of symptoms was lower using ‘4-of-7’ (18·2±12·0 vs 23±12·0, P=0·08) or ‘1-of-1’ (20·4±12·4 vs 23±12·0, P=0·07) than ‘standard’ onset criteria. Severity of arrhythmia tended to be less with either ‘4-of-7’ (16±10·4 vs 19·1±19·4, P=0·12) or ‘1-of-1’ (17·5±10·3 vs 19·1±9·4, P=0·18) than with ‘standard’ onset criteria. Conclusions The more sensitive onset criteria for detection of atrial tachyarrhythmias were associated with lower frequency and severity of symptoms.

Recent reports suggest that cardiac pacing incorporating a rate-drop response algorithm is associated with a reduction in the frequency of syncopal episodes in patients with apparent cardioinhibitory vasovagal syncope. The detection portion of the algorithm employs a programmable heart rate change-time duration "window" to both identify abrupt cardiac slowing suggestive of an imminent vasovagal event and trigger "high rate" pacing. The purpose of this study was to develop recommendations for programming the rate-drop response algorithm. Pacemaker programming, symptom status, and drug therapy were assessed retrospectively in 24 patients with recurrent vasovagal syncope of sufficient severity to warrant consideration of pacemaker treatment. In the 53 +/- 19 months prior to pacing, patients had experienced an approximate syncope burden of 1.2 events/month. During follow-up of 192 +/- 160 days, syncope recurred in 4 patients (approximate syncope burden, 0.3 events/month, p 100 beats/min in 89% of patients, with a duration of 1 to 2 min in 79%. In conclusion, a narrow range of rate-drop response parameter settings appeared to be effective for most individuals in this group of highly symptomatic patients.

Current anchoring systems on pacemaker leads are crude in comparison to the lead technology. Poor anchoring technique may cause damage to the lead or early displacement from incorrect suture tension. We describe experience with a locking anchoring sleeve that applies a constant gripping force to the lead body. This can be locked and unlocked to allow optimal positioning after fixation of the sleeve to underlying tissues. The sleeve was fitted to a 55D polyurethane lead (Medtronic 4024, 7 Fr, bipolar, steroid eluting) implanted in the ventricular position in 22 patients at four European centers. All implants were uncomplicated; data were collected on handling and ease of use. Assessments were made using a scale of 1-10 (10 = excellent, 5 = equivalent to conventional sleeve). Overall ease of use compared to conventional sleeve was 7.79 +/- 0.62 (mean +/- SD). Mean scoring of flexibility of the lead at the transition points was 7.92 +/- 0.72; ability to lock/unlock the sleeve scored 6.28 +/- 1.78. Ease of suturing around the sleeve scored 8.07 +/- 0.77, and ability to slide the sleeve along the lead body scored 6.48 +/- 1.99. Chest X rays at 6 weeks showed no change in lead position with respect to postimplant films, and all leads showed a straight path on either side of the sleeve with no evidence of conductor distortion. Follow-up to 3 years has been without problem. All leads remain intact and in place, with stable thresholds and no evidence of erosion. There have been no complaints of patient discomfort. We conclude that this device is safe and effective and offers a significant advance in lead fixation.

This study examined the effectiveness of cardiac pacing using the Thera DR rate-drop response algorithm for prevention of recurrent symptoms in patients with carotid sinus syndrome (CSS) or vasovagal syncope. The algorithm comprises both diagnostic and treatment elements. The diagnostic element consists of a programmable "window" used to identify heart rate changes compatible with an evolving neurally mediated syncopal episode. The treatment arm consists of pacing at a selectable rate and for a programmable duration. Forty-three patients (mean age 53 +/- 20.4 years) with CSS alone (n = 8), CSS in conjunction with vasovagal syncope (n = 4), or vasovagal syncope alone (n = 31) were included. Thirty-nine had recurrent syncope, while the remaining four reported multiple presyncopal events. Prior to pacing, 40 +/- 152 syncopal episodes (range from 1 to approximately 1,000 syncopal events) over the preceding 56 +/- 84.5 months. Postpacing follow-up duration was 204 +/- 172 days. Three patients have been lost to follow-up and in one patient the algorithm was disabled. Among the remaining 39 individuals, 31 (80%) indicated absence or diminished frequency of symptoms, or less severe symptoms. Twenty-three patients (23/29, or 59%) were asymptomatic with respect to syncope or presyncope. Sixteen patients had symptom recurrences. Of these, seven experienced syncope (7/39, or 18%) and 9 (29%) had presyncope: the majority of patients with recurrences (6/7 syncope and 7/9 presyncope) were individuals with a history of vasovagal syncope. Consequently, although symptoms were observed during postpacing follow-up, they appeared to be of reduced frequency and severity. Thus, our findings suggest that a transient period of high rate pacing triggered by the Thera DR rate-drop response algorithm was beneficial in a large proportion of highly symptomatic patients with CSS or vasovagal syncope.

OBJECTIVES: To define the effects of long-term thyroxine treatment upon heart rate, blood pressure, left ventricular systolic function, and left ventricular size, as well as indices of autonomic function, and to compare findings with those in patients with thyrotoxicosis before and during treatment. DESIGN: Cross sectional study of patients prescribed thyroxine long term (n = 11), patients with thyrotoxicosis studied at presentation (n = 23), compared with controls (n = 25); longitudinal study of patients with thyrotoxicosis studied at presentation and serially after beginning antithyroid drug treatment (n = 23). METHODS: 24 h ambulatory monitoring of pulse and blood pressure, echocardiography, forearm plethysmography, and autonomic function tests. RESULTS: Long-term thyroxine treatment in doses that reduced serum thyrotrophin to below normal had no effect on blood pressure, heart rate, left ventricular systolic function or stroke volume index, but was associated with an 18.4% increase in left ventricular mass index (mean (SEM) 101.9 (3.09) g/m2 v controls 86.1 (4.61), P < 0.01). Thryoxine treatment, like thyrotoxicosis, had no effect on tests of autonomic function. Untreated thyrotoxicosis resulted in pronounced changes in systolic and diastolic blood pressure and an increase in heart rate during waking and sleep. Patients with thyrotoxicosis at presentation had an increase in left ventricular systolic function (ejection fraction 70.5 (1.66)% v 65.4 (1.79), P < 0.01; fractional shortening 40.4 (1.54)% v 35.6 (1.46), P < 0.01), increased stroke volume index (45.9 (2.4) ml/m2 v 36.6 (1.7), P < 0.001), and an increase in forearm blood flow, and decrease in vascular resistance. They had a similar degree of left ventricular hypertrophy to that associated with thyroxine treatment (99.3 (4.03) g/m2); all changes were corrected within 2 months by antithyroid drugs. CONCLUSIONS: The development of left ventricular hypertrophy in patients receiving thyroxine in the absence of significant changes in heart rate, blood pressure, and left ventricular systolic function is consistent with a direct trophic effect of thyroid hormone on the myocardium. The presence of left ventricular hypertrophy determines that further studies are essential to assess cardiovascular risk in patients taking thyroxine long term.

The ability of externally strapped accelerometer- (Excel [Cardiac Pacemakers, Inc.]) and vibration-based (Activitrax [Medtronic, Inc.]) rate adaptive pacemakers to reproduce the rate response of the same implanted devices with identical programming was evaluated in ten patients by ambulatory Holter monitoring. The resting and postexercise external pacemaker rates closely resembled those of the respective implanted devices. During short bursts and more prolonged exercise, both types of strapped-on devices underestimated maximal implanted pacemaker rate response by 4%-10% when programmed to nominal rate adaptive settings. Studies evaluating chronotropic responses from either type of externally strapped activity sensor appear valid, provided the modest attenuation in maximal rate increase by this method is appreciated.

The evolution of upright posture is usually considered an advantage in humans. For people with postural tachycardia syndrome (PoTS) it can present a daily challenge. Although orthostatic intolerance is often associated with older people, PoTS tends to affect young women who present with multiple, non-specific symptoms and significant functional impairment.1 PoTS was characterised in 1993,2 but previously existed under various names including irritable heart, soldier's heart, and idiopathic orthostatic intolerance. It is a heterogeneous group of disorders sharing similar characteristics as a consequence of abnormal autonomic nervous system response to assuming upright posture. When humans stand up, approximately 500 ml of blood descends from the thorax into the abdominal cavity and limbs. A normal autonomic nervous system responds with immediate peripheral vasoconstriction, increase in heart rate of 10–20 beats per minute (bpm), and minimal change in blood pressure.1 In patients with PoTS this mechanism does not respond appropriately; the exact pathophysiology remains unclear.3 A likely mechanism is inadequate vasoconstriction on standing, resulting in pooling of blood in splanchnic and peripheral vasculature. Heart rate and catecholamine levels increase further to compensate. Symptoms of cerebral hypoperfusion including dizziness and syncope occur, often in the presence of normal blood pressure. Ironically, some patients with PoTS have a hypertensive response to standing.1 Diagnosis is usually made following a tilt table test or 10-minute stand test. The definition is arbitrary, but agreed by consensus (Box 1).4 Heart rate increases but, by definition, blood pressure does not necessarily drop. However, there is overlap with neurally mediated hypotension and some …

Background — Amiodarone-induced thyrotoxicosis (AIT) is a difficult management problem about which there are little published data. We examined whether continuing amiodarone or differentiating AIT into 2 subtypes affected outcome. Methods and Results — The type and duration of antithyroid treatment and response were recorded in a consecutive series of 28 cases. Comparisons were made between those in whom amiodarone either was continued or stopped and between those with either possible type 1 or type 2 AIT. Of the 28 cases, 5 had spontaneous resolution of AIT; 23 received carbimazole (CBZ) alone as first-line therapy. Eleven achieved long-term euthyroidism off CBZ or on a maintenance dose. Five became hypothyroid and required long-term thyroxine. Five relapsed after stopping CBZ treatment and were rendered euthyroid with either long-term CBZ (n=3) or radioiodine (n=2). Four were intolerant of CBZ and received propylthiouracil (PTU), with good effect in 3. One was resistant to thionamide alone (CBZ then PTU) and responded to adjunctive steroids. No difference in presentation or outcome was noted between those in whom amiodarone was continued or stopped or between possible type 1 or type 2 AIT. Conclusions — Continuing amiodarone has no adverse influence on response to treatment of AIT. First-line therapy with a thionamide alone is appropriate in iodine-replete areas, thus avoiding potential complications of other drugs. Differentiating between 2 possible types of AIT does not influence management or outcome.

This article contains an overview of the pathophysiology and aetiological factors in angina pectoris, and a review of current strategies for the management of the patient with both stable and unstable angina. In particular, the role of contemporary revascularisation therapy in angina (aorto-coronary bypass surgery or coronary angioplasty) is analysed.

In the early 1950s, Dr Aubrey Leatham established a cardiac unit at St. George's Hospital, Hyde Park Corner, London. He developed and taught the essential clinical skill of cardiac auscultation. Under his guidance a clinical department for the care of cardiac patients was developed and coupled to physiological academic research. He was a pioneer in cardiac pacing and, in 1961, Harold Siddons, O'Neal Humphries, and Aubrey Leatham implanted the first 'indwelling' pacemaker in the UK in a 65-year-old man with repeated Stokes-Adams attacks due to complete heart block. The nickel-cadmium 'accumulator', which powered the pacemaker, had to be recharged once a week.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Drugs slowing electocardiographic QT conduction can cause tachyarrhythmias, torsades de pointes (TdP) and cardiac arrest. • Associated risks of sudden death have been consistently found for older, typical, antipsychotic drugs, but epidemiological evidence of risks for other drugs are poorly defined. WHAT THIS STUDY ADDS • In a population-based study risk of sudden death with noncardiac drug treatment was mainly posed by antipsychotics both typical and atypical, and by antidepressants, particularly selective serotonin reuptake inhibitors. • Results could not be accounted for by confounding. • No significant risk was associated with use of other noncardiac or psychiatric drugs. • A published general categorization of risk of drug-induced TdP corresponded poorly with these findings. AIMS To examine risks of sudden death in the community associated with drugs grouped by their risk of causing torsades de pointes (TdP) and to explore the risks for individual drugs. METHODS Case–control study comparing prior drug intakes and morbidities, using the Arizona classification of drugs causing TdP. Participants included 1010 patients dying suddenly where post-mortem examination did not identify a clear cause of death, and 3030 matched living controls from primary care. RESULTS Noncardiac drug risk was posed by antipsychotics and antidepressants. Significantly raised odds ratios (ORs) were found for takers of typical and atypical antipsychotics, ORs [95% confidence interval] 3.94 (2.05, 7.55) and 4.36 (2.54, 7.51), and of selective serotonin reuptake inhibitors [SSRIs] rather than tricyclic antidepressants, ORs 2.21 (1.61, 3.05) and 1.44 (0.96, 2.13). No significant risk was associated with other, noncardiac or psychiatric drugs, OR 1.09 (0.85, 1.41). Arizona classified drugs considered to raise risk of TdP were associated with raised risk of sudden death, as were those only weakly associated with TdP and not considered to pose a risk in normal use, ORs 2.08 (1.45, 3.00) and 1.74 (1.33, 2.28), respectively. CONCLUSIONS Atypical and typical antipsychotic drug use were both strongly associated with raised risks, as were SSRIs. Tricyclic antidepressants were not associated with raised risks. The Arizona classification of risk of TdP was a poor predictor of likelihood of noncardiac drug-associated sudden death.

BACKGROUND: Previous studies have suggested that minor changes in thyroid function are associated with risk of atrial fibrillation (AF). Our objective was to determine the relationship between thyroid function and presence of atrial fibrillation (AF) in older subjects. METHODS: A population-based study of 5860 subjects 65 years and older, which excluded those being treated for thyroid dysfunction and those with previous hyperthyroidism. Main outcome measures included tests of thyroid function (serum free thyroxine [T(4)] and thyrotropin [TSH]) and the presence of AF on resting electrocardiogram. RESULTS: Fourteen subjects (0.2%) had previously undiagnosed overt hyperthyroidism and 126 (2.2%), subclinical hyperthyroidism; 5519 (94.4%) were euthyroid; and 167 (2.9%) had subclinical hypothyroidism and 23 (0.4%), overt hypothyroidism. The prevalence of AF in the whole cohort was 6.6% in men and 3.1% in women (odds ratio, 2.23; P

This study sought to prospectively evaluate the prevalence of cardiovascular abnormalities in patients with overt hyperthyroidism before and after antithyroid therapy.Overt hyperthyroidism is associated with recognized cardiovascular effects believed to be reversed by antithyroid therapy; however, increasing data suggest significant long-term cardiovascular mortality.A total of 393 (312 women, 81 men) consecutive unselected patients with overt hyperthyroidism were recruited and compared with 393 age- and gender-matched euthyroid control subjects. Hyperthyroid patients were re-evaluated after antithyroid therapy. Findings in patients and matched control subjects were compared at presentation, after treatment when patients had subclinical hyperthyroidism biochemically, and when patients were rendered biochemically euthyroid. All had a structured cardiovascular history and examination, including measurements of blood pressure (BP) and pulse rate. All had resting 12-lead electrocardiogram and 24-h digital Holter monitoring of cardiac rhythm.A higher prevalence of cardiovascular symptoms and signs, as well as abnormal hemodynamic parameters, was noted among hyperthyroid patients at recruitment compared with control subjects. Cardiac dysrhythmias, especially supraventricular, were more prevalent among patients than among control subjects. Palpitation and dyspnea, postural decrease in systolic pressure, and atrial fibrillation (AF) remained more prevalent in treated hyperthyroid subjects with subclinical hyperthyroidism compared with control subjects, and remained more prevalent after restoration of euthyroidism. Predictors for successful reversion to sinus rhythm in those with AF associated with hyperthyroidism were lower BP measurements at recruitment and an initial hypothyroid state induced by antithyroid therapy. Mortality was higher in hyperthyroid subjects than in control subjects after a mean period of follow-up of 66.6 months.Cardiovascular abnormalities are common in patients with overt hyperthyroidism at presentation, but some persist despite effective antithyroid therapy.

Tilt testing is accepted as the main tool for the diagnosis of neurocardiogenic syncope, particularly in the "malignant" vasovagal form. As a result of experience with tilt testing, the cardiovascular responses to head-up tilting in patients with malignant vasovagal syncope (MVVS) have been defined in respect of the vasodepressor (hypotensive) and cardioinhibitory (bradycardic) components. Pacing therapy has been of limited value in the past, with controversy about its role, even in the cardioinhibitory form of MVVS. With the advent of more sophisticated algorithms for pacing (i.e., rate-drop response [RDR], Thera DR) in response to the onset of bradycardia in MVVS, however, this therapy is being reexamined. This article examines the blood pressure and heart rate responses to head-up tilt in patients with MVVS and examines the role of this test in screening such patients for the benefits of pacing with RDR. Careful analysis of the pattern of blood pressure and heart rate response during the tilt test may allow selection of those patients likely to respond to RDR and may provide useful information for initial programming of the algorithm.

Aims Left ventricular (LV) and biventricular (BiV) pacing are potentially superior to right ventricular (RV) apical pacing in patients undergoing atrioventricular (AV) junction ablation and pacing for permanent atrial fibrillation. Methods and results Prospective randomized, single-blind, 3-month crossover comparison between RV and LV pacing (phase 1) and between RV and BiV pacing (phase 2) performed in 56 patients (70±8 years, 34 males) affected by severely symptomatic permanent atrial fibrillation, uncontrolled ventricular rate, or heart failure. Primary endpoints were quality of life and exercise capacity. Compared with RV pacing, the Minnesota Living with Heart Failure Questionnaire (LHFQ) score improved by 2 and 10% with LV and BiV pacing, respectively, the effort dyspnoea item of the Specific Symptom Scale (SSS) changed by 0 and 2%, the Karolinska score by 6 and 14% ( P

Amiodarone-induced thyrotoxicosis (AIT) is a difficult management problem about which there are little published data. We examined whether continuing amiodarone or differentiating AIT into 2 subtypes affected outcome.The type and duration of antithyroid treatment and response were recorded in a consecutive series of 28 cases. Comparisons were made between those in whom amiodarone either was continued or stopped and between those with either possible type 1 or type 2 AIT. Of the 28 cases, 5 had spontaneous resolution of AIT; 23 received carbimazole (CBZ) alone as first-line therapy. Eleven achieved long-term euthyroidism off CBZ or on a maintenance dose. Five became hypothyroid and required long-term thyroxine. Five relapsed after stopping CBZ treatment and were rendered euthyroid with either long-term CBZ (n=3) or radioiodine (n=2). Four were intolerant of CBZ and received propylthiouracil (PTU), with good effect in 3. One was resistant to thionamide alone (CBZ then PTU) and responded to adjunctive steroids. No difference in presentation or outcome was noted between those in whom amiodarone was continued or stopped or between possible type 1 or type 2 AIT.Continuing amiodarone has no adverse influence on response to treatment of AIT. First-line therapy with a thionamide alone is appropriate in iodine-replete areas, thus avoiding potential complications of other drugs. Differentiating between 2 possible types of AIT does not influence management or outcome.

Thyrotoxicosis is often perceived as a reversible disorder without long-term consequences, perhaps because of the availability of effective treatments, but recent evidence suggests that there may, in fact, be adverse outcomes. Long-term follow-up studies have revealed increased mortality from cardiovascular and cerebrovascular disease in those with a past history of overt hyperthyroidism treated with radioiodine as well as in those with subclinical hyperthyroidism indicated by a low serum TSH concentration. Thyroid hormones exert direct effects on the myocardium as well as the systemic vasculature predisposing to dysrhythmias, especially supraventricular. Effects of thyroid hormones on the autonomic nervous system may also contribute to arrhythmogenesis. Atrial fibrillation is a recognized complication of hyperthyroidism that predisposes to embolic events. Development of atrial fibrillation, together with other supraventricular dysrhythmias (both clinically obvious and those detected only by Holter monitoring) in those with hyperthyroidism may account for increased vascular mortality. Improved detection of supraventricular dysrhythmias and therapeutic intervention (e.g. anticoagulants, antiarrhythmics) may improve the long-term vascular prognosis, but their role remains to be established in large therapeutic trials.

Introduction: Previous studies have suggested that long-term right ventricular apex (RVA) pacing causes dyssynchronous left ventricular (LV) contraction, promoting heart failure and increasing mortality. Placing a lead against the right ventricular high septum (RVHS) allows closer proximity to the His-Purkinje system and therefore may allow more physiological depolarisation of the left ventricle. However, recent clinical studies regarding the influence of pacing sites on LV function have produced conflicting results. Objectives: We hypothesized that RVA pacing would worsen myocardial deformation more than than RVHS pacing. Methods: In this multicenter, randomized controlled trial of 240 pts (74 11yrs, 67% males) with preserved LVEF and implanted pacemaker due to high grade atrioventricular block, deformation imaging was possible in 148 pts, of whom 78 were randomized to RVA and 70 to RVHS. We measured LVEF and global longitudinal strain (GLS) using speckle tracking (EchoPAC PC BT11: GE Healthcare, QLAB version 9.1: Philips Medical Systems) at baseline (post pacemaker implantation) and at two years. Results: In the RVA group, the mean LVEF at baseline was 56.8 8.5% and at two years was 53.6 9.6 (p1⁄40.002) and in the RVHS baseline LVEF was 55.8 10.1 and at two years 53.2 10.4 (p1⁄40.013). In the RVA group, the mean GLS at baseline was -15.9 4.0% and at two years was -13.9 4.0 (p

Dr Faizel Osman and colleagues (July 2001 JRSM, pp. 346-348) present two cases of thyrotoxicosis with heart block. For the second patient, who responded well only to steroid therapy, they raise the question whether the triad of thyrotoxicosis, heart block and raised erythrocyte sedimentation rate could be due to a single autoimmune disease; yet they do not say whether this was investigated or not.

All patients with permanent AF in whom a clinical decision has been made to undertake complete AV junctional ablation and ventricular pacing (conventional indication for ‘ablate and pace’) Patients with permanent AF, drug-refractory heart failure, uncontrolled ventricular rate and left bundle branch block (LBBB) pattern or non-specific intraventricular conduction defect (IVCD) (QRS 150 ms) in whom a clinical decision has been made to undertake left ventricular synchronization pacing (consistent with previous investigational indications for BiV pacing).

There can be little doubt that frequent, recurrent syncope has a significant impact on quality of life (QoL) for the majority of sufferers;1 this impact ranges from effects on education in the young, through impaired social life and ability to drive in adolescence, curtailed career opportunities in adult life and risk of fractures and other injuries in later years. But, does the ability to measure that impact translate into an improvement in management options and hence improved QoL in patients with syncope? Many studies have examined the therapeutic approaches to syncope; most have included assessment of QoL as part of their endpoints, but the tools used to measure QoL are varied and may not be sufficiently sensitive or specific to enable evaluation of the impact on individual patients and subsequent assessment of overall benefit from a management strategy. Scales such as the … *Corresponding author. Tel: +44 121 415 8033, Fax: +44 121 414 7194, Email: m.d.gammage{at}bham.ac.uk

This editorial refers to 'Selective-site pacing in paediatric patients: a new application of the Select Secure system' by F. Cantuet al., on page 601 While the debate about the role of selective site pacing in adults with structurally normal hearts continues, many in the paediatric pacing fraternity have adopted the new technologies available with open arms as a means to address some of the long-standing difficulties associated with pacing infants, children, and young adults. The chal- lenges for endocardial pacing in the paediatric population are many, but include unusual anatomy, smaller access vessels, need for active fixation, need for good manoeuvrability of the lead/delivery system, ability to deal with growth and leads with very high expectations of longevity and reliability. In many ways, a new catheter-delivered

Background —Atrioventricular (AV) node ablation and pacing has become accepted therapy for drug-refractory paroxysmal atrial fibrillation (PAF). However, few data demonstrate its superiority over continued medical therapy. The influence of pacing mode and mode-switch algorithm has not been investigated. Methods and Results —Symptomatic patients who had tried ≥2 drugs for PAF were randomized to continue medical therapy (n=19) or AV junction ablation and implantation of dual-chamber mode-switching (DDDR/MS) pacemakers (slow algorithm [n=19] or fast algorithm [n=18]). Follow-up over 18 weeks was at 6-week intervals and used quality-of-life questionnaires (Psychological General Well Being [PGWB], McMaster Health Index [MHI], cardiac symptom score), exercise testing, echocardiography, and Holter monitoring. Paced patients were randomized to DDDR/MS or VVIR and subsequently crossed over. Ablation and DDDR/MS pacing produced better scores than drug therapy for overall symptoms (−41%, P P =0.0001), and dyspnea (−37%, P P P P P P P P P Conclusions —Ablation and DDDR/MS pacing produces more symptomatic benefit than medical therapy or ablation and VVIR pacing but may result in early development of persistent AF.

Pacing for the relief of bradycardia might be considered a ‘mature’ therapy, having now been available for 50 years, so it is refreshing to see that there are still many unanswered questions relating to the practice of pacing the ventricle. Although it seems clear from population-based studies that ventricular pacing increases the risk of left ventricular dysfunction and that the cumulative percentage of pacing is directly related to that risk,1 it is unclear whether it is simply pacing the ventricle or the site of ventricular pacing that is the real problem. Perhaps, the most compelling evidence that right ventricular (RV) apical pacing may be deleterious came from the DAVID study2 which compared back-up VVI pacing at 40 ppm and DDDR pacing at 70 ppm. The VVI group did not require much ventricular pacing compared with the DDDR group. Although many patients had impaired LV function, only 12% had NYHA class III or IV symptoms and patients who were paced more frequently were more likely to have an adverse outcome in terms of heart failure. The debate about RV pacing is further confused by clinical anecdote (many patients seem to remain perfectly well despite RV apical pacing) and variable results from previous studies.3–5 These discrepancies have usually been put down to duration of pacing, differences in study design, variation in pacing site studied, and inadequate duration of …

As the indications for implantable cardiac devices [pacemakers, cardioverter-defibrillators (ICDs), and cardiac resynchronization systems (CRT)] have been extended over the last decade, the need for elective external cardioversion (ECV) in patients with such devices and concurrent atrial fibrillation (AF) has also increased. In addition, the overall requirement for ECV has also been extended by the increasing age of the population in most developed countries and a more aggressive approach to the management of recent-onset and haemodynamically compromising AF.1 The use of ECV in patients with implanted devices has long been a cause for concern with regard to the potential for adverse effects on the generator and/or leads, with the result that this simple and effective therapy may have been delayed or even denied to some patients. These concerns were largely fuelled by a number of reports in the 1970s and 1980s suggesting the potential for device interference or lead failure.2,3 Devices implanted within the last decade, however, are considerably more sophisticated, more likely to use bipolar lead configurations, and better protected against external interference than those of the period from which these reports arose, leaving the question of safety in patients with modern implantable devices open. In addition, ECV has evolved over recent years with the development of equipment able to deliver biphasic shocks resulting in an increased efficacy and lower energy requirements. As CRT has … Corresponding author. Tel: +44 121 697 8338; fax: +44 121 414 3713. E-mail address : m.d.gammage{at}bham.ac.uk

A 31-year-old woman had suffered with depression for several years. In January 2000, she was commenced on Venlafaxine 75 mg BD. She started to complain of palpitation following titrating up of her Venlafaxine therapy to 75mgTDS in March 2001. Eventually, she stopped her Venlafaxine therapy in September 2001 due to recurrent palpitation. Unfortunately, she started to experience a significant deterioration in her mood and depression disorder without any response to other antidepressants. As a result, she was recommenced again on Venlafaxine 75 mg OD in February 2002. She did not develop any symptoms of palpitation on this dose. However, she started to develop palpitation again on titrating her Venlafaxine dose to 75 mg BD in July 2004. She was reviewed in the cardiology outpatient clinic inMarch 2005 where she continued to complain of recurrent regular palpitation. She did not complain of breathlessness, orthopnea, or paroxysmal nocturnal dyspnoea. There was no history of warning symptoms and no other precipitating factors. She had no past medical history of heart or thyroid disease and she was not on any other regular medications. She drank very little alcohol but suffered with mild asthma. Physical examination was completely unremarkable apart from resting sinus tachycardia at 120 beats per minute. There were no signs of underlying cardiac disease or thyroid disease. Her ECG confirmed the presence of sinus tachycardia with no other significant abnormalities. Her echocardiogram was completely normal as were her blood tests including thyroid function. The patient was very reluctant to stop her Venlafaxine and was prescribed Verapamil for symptom control. She later