Incremental value of left atrial structural and functional characteristics for prediction of atrial fibrillation in patients receiving cardiac pacing.

BACKGROUND: Better prediction of cardiac pacing patients at risk of atrial fibrillation (AF) would enable more effective prophylaxis. We sought whether left atrial (LA) electromechanical conduction time (EMT) and myocardial mechanics were associated with incident AF in patients undergoing dual chamber pacemaker implantation, independent of left atrial volume (LAV). METHODS AND RESULTS: Clinical data were obtained prospectively in 146 enrollees (73±10 years) undergoing dual chamber pacemaker implantation in the Protect-Pace study. Echocardiograms and 2-dimensional strain analysis were obtained post implantation and at 2 years. Complete ascertainment of AF during follow-up was identified from interrogation of permanent pacemakers. Cox regression was used to identify correlates of AF. Incident AF (n=29, 20%) was associated with higher systolic blood pressure (P=0.01), lower left ventricular ejection fraction (P=0.03), lower LA strain at atrial contraction (LASac; P<0.001), higher LAV (P<0.003), and longer septal electromechanical conduction time (P<0.01). The associations of LAV and LASac with incident AF were independent of age, sex, systolic blood pressure, and left ventricular size and function. However, the combination of the 3 strongest predictors showed LASac (P=0.02) and systolic blood pressure (P=0.01) were independently associated with incident AF, but LAV was not (P=0.07). Using the optimal cut points from receiver operator characteristic curves (62 mL for LAV and 8.6% for LASac), we demonstrated that a significantly greater rate of AF was associated with both lower LASac at higher LAV and with lower LASac at lower LAV. CONCLUSIONS: The risk of AF in patients receiving dual chamber pacing is independently associated with LA size and function, not left ventricular structural and functional characteristics or right ventricular lead location. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00461734.

Dyssynchrony, contraction efficiency and regional function with apical and non-apical RV pacing.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 p < 0.01). 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. CONCLUSIONS: Inefficient dyssynchronous contraction and the decrease in apical strain appear to be associated with global LV impairment in RVA. TRIAL REGISTRATION NUMBER: PROTECT-PACE ClinicalTrials.gov number NCT00461734.

Effect of right ventricular pacing lead site on left ventricular function in patients with high-grade atrioventricular block: results of the Protect-Pace study.

AIM: Chronic right ventricle (RV) apical (RVA) pacing is standard treatment for an atrioventricular (AV) block but may be deleterious to left ventricle (LV) systolic function. Previous clinical studies of non-apical pacing have produced conflicting results. The aim of this randomized, prospective, international, multicentre trial was to compare change in LV ejection fraction (LVEF) between right ventricular apical and high septal (RVHS) pacing over a 2-year study period. METHODS AND RESULTS: We randomized 240 patients (age 74 ± 11 years, 67% male) with a high-grade AV block requiring >90% ventricular pacing and preserved baseline LVEF >50%, to receive pacing at the RVA (n = 120) or RVHS (n = 120). At 2 years, LVEF decreased in both the RVA (57 ± 9 to 55 ± 9%, P = 0.047) and the RVHS groups (56 ± 10 to 54 ± 10%, P = 0.0003). However, there was no significant difference in intra-patient change in LVEF between confirmed RVA (n = 85) and RVHS (n = 83) lead position (P = 0.43). There were no significant differences in heart failure hospitalization, mortality, the burden of atrial fibrillation, or plasma brain natriutetic peptide levels between the two groups. A significantly greater time was required to place the lead in the RVHS position (70 ± 25 vs. 56 ± 24 min, P < 0.0001) with longer fluoroscopy times (11 ± 7 vs. 5 ± 4 min, P < 0.0001). CONCLUSION: In patients with a high-grade AV block and preserved LV function requiring a high percentage of ventricular pacing, RVHS pacing does not provide a protective effect on left ventricular function over RVA pacing in the first 2 years. PROTECT-PACE: ClinicalTrials.gov number NCT00461734.

Guidelines for the diagnosis, prevention and management of implantable cardiac electronic device infection. Report of a joint Working Party project on behalf of the British Society for Antimicrobial Chemotherapy (BSAC, host organization), British Heart Rhythm Society (BHRS), British Cardiovascular Society (BCS), British Heart Valve Society (BHVS) and British Society for Echocardiography (BSE).

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.

Aubrey Leatham and the introduction of cardiac pacing to the UK.

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.

Sudden death in patients receiving drugs tending to prolong the QT interval.

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.

Treatment of amiodarone-associated thyrotoxicosis.

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.

Cardiovascular manifestations of hyperthyroidism before and after antithyroid therapy: a matched case-control study.

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.

Prevalence of subclinical thyroid dysfunction and its relation to socioeconomic deprivation in the elderly: a community-based cross-sectional survey.

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 T4 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.

Multi-center clinical experience with a lumenless, catheter-delivered, bipolar, permanent pacemaker lead: implant safety and electrical performance.

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.

Clinicians didn't reliably distinguish between different causes of cardiac death using case histories.

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.