Defibrillation testing at the time of ICD insertion: an analysis from the Ontario ICD Registry.

BACKGROUND: increasingly, ICD implantation is performed without defibrillation testing (DT). OBJECTIVES: To determine the current frequency of DT, the risks associated with DT, and to understand how physicians select patients to have DT. METHODS: between January 2007 and July 2008, all patients in Ontario, Canada who received an ICD were enrolled in this prospective registry. RESULTS: a total of 2,173 patients were included; 58% had new ICD implants for primary prevention, 25% for secondary prevention, and 17% had pulse generator replacement. DT was carried out at the time of ICD implantation or predischarge in 65%, 67%, and 24% of primary, secondary, and replacement cases respectively (P = <0.0001). The multivariate predictors of a decision to conduct DT included: new ICD implant (OR = 13.9, P < 0.0001), dilated cardiomyopathy (OR = 1.8, P < 0.0001), amiodarone use (OR = 1.5, P = 0.004), and LVEF > 20% (OR = 1.3, P = 0.05). A history of atrial fibrillation (OR = 0.58, P = 0.0001) or oral anticoagulant use (OR = 0.75, P = 0.03) was associated with a lower likelihood of having DT. Age, gender, NYHA class, and history of stroke or TIA did not predict DT. Perioperative complications, including death, myocardial infarction, stroke, tamponade, pneumothorax, heart failure, infection, wound hematoma, and lead dislodgement, were similar among patients with (8.7%) and without (8.3%) DT (P = 0.7) CONCLUSIONS: DT is performed in two-thirds of new ICD implants but only one-quarter of ICD replacements. Physicians favored performance of DT in patients who are at lower risk of DT-related complications and in those receiving amiodarone. DT was not associated with an increased risk of perioperative complications.

Advances in the treatment of atrial fibrillation.

Management of atrial fibrillation (AF) has changed greatly in the past 10 years. The advent of a greater understanding of the pathophysiology of AF has resulted in major therapeutic breakthroughs, both in invasive and non-invasive strategies. New antiarrhythmic agents with fewer side effects, new anticoagulants and technical advances in ablation have changed the treatment of this condition. Molecular modification of the highly effective amiodarone, to improve safety and tolerability, has produced promising analogues such as Dronedarone. Although this drug seems less effective than amiodarone in preventing AF recurrence, the drug presented an interesting data on reduction of stroke and cardiovascular death, a novel effect that needs further investigation. New antiarrhythmics with atria selectiveness such Vernakalant, might be useful for cardioversion in AF without ventricular proarrhythmia. Dabigatran, a prodrug that directly inhibits thrombin, represents an alternative to warfarin for anticoagulant treatment in selected patients. In AF ablation, technological advances are sure to result in the necessary improvements in the safety and procedures efficacy. These technologies include ablation catheters designed to electrically isolate the pulmonary veins with improved safety, efficacy, speed, and precision and improved imaging and electrical mapping systems. Although pulmonary vein isolation remains essential for most ablation procedures, the role of substrate modification has taken on increasing importance. In this article, we review the advances in the treatment of AF, focus on the new medications and advances in invasive procedures.

Treating the right patient at the right time: access to heart failure care.

Heart failure affects over 500,000 Canadians, and 50,000 new patients are diagnosed each year. The mortality remains staggering, with a five-year age-adjusted rate of 45%. Disease management programs for heart failure patients have been associated with improved outcomes, the use of evidence-based therapies, improved quality of care, and reduced costs, mortality and hospitalizations. Currently, national benchmarks and targets for access to care for cardiovascular procedures or office consultations do not exist. The present paper summarizes the currently available data, particularly focusing on the risk of adverse events as a function of waiting time, as well as on the identification of gaps in existing data on heart failure. Using best evidence and expert consensus, the present article also focuses on timely access to care for acute and chronic heart failure, including timely access to heart failure disease management programs and physician care (heart failure specialists, cardiologists, internists and general practitioners).

Medical and surgical management of early Q wave myocardial infarction. I. Effects of surgical reperfusion on survival, recurrent myocardial infarction, sudden death and functional class at 10 or more years of follow-up.

To define the outcome of patients given medical or surgical therapy for Q wave myocardial infarction, 387 patients were followed up for 10 to 13 years (mean 11.4). On study entry the groups had similar distributions for variables such as mean age, gender, previous myocardial infarction, abnormal creatine kinase activity, area of infarction, number of vessels diseased and clinical classification. The hospital mortality rate of the medical versus surgical group was 11.5% (23 of 200) versus 5.8% (11 of 187) (p = 0.07). Early reperfusion (that is, less than or equal to 6 h) resulted in a lower mortality rate than did medical therapy--2% (2 of 100) versus 11.5% (23 of 200) (p less than 0.05)--whereas the hospital mortality rate with late reperfusion was 10.3% (9 of 87). The long-term mortality rate of the medical and surgical groups was 41% (82 of 200) versus 27% (51 of 187) (p = 0.0007) with use of an adjusted Cox proportional hazards model. In the survivors, the differences between medical and surgical groups in recurrent myocardial infarction, mortality associated with reinfarction and sudden death were prospectively followed and evaluated by the life table method. Recurrent myocardial infarction was not prevented by surgical reperfusion or medical therapy (23% in both groups), however, the mortality rate in patients with recurrent infarction was higher in the medical therapy group--36.6% (15 of 41) versus 17.5% (7 of 40) (p = 0.04). The mortality difference did not depend on early or late surgical reperfusion. In the in-hospital survivors, the incidence of sudden death was 17.5% in the medical (31 of 177) versus 7.4% (13 of 176) in the surgical group (p = 0.01). This difference was much more pronounced in the early reperfusion group. Functional class was significantly lower than that for medical therapy in the early reperfusion but not the late reperfusion group. Thus, in comparable groups given medical and surgical therapy for acute myocardial infarction and followed up for greater than or equal to 10 years, surgical reperfusion appears to offer improved longevity in selected cases (when implemented early) but does not prevent recurrent myocardial infarction. The associated mortality with recurrent myocardial infarction is less as is the incidence of sudden death. Finally, lower functional class occurs most often in patients given early reperfusion.

Treating the right patient at the right time: access to care in non-ST segment elevation acute coronary syndromes.

In 2004, the Canadian Cardiovascular Society formed an Access to Care Working Group with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary discusses the rationale for access benchmarks for urgent cardiac catheterization and revascularization, including hospital transfer in the setting of non-ST elevation acute coronary syndromes. The literature on standards of care, wait times, wait list management and clinical trials was reviewed. A survey of all cardiac catheterization directors in Canada was performed to develop an inventory of current practices in identifying and triaging patients. The Working Group recommended the following medically acceptable wait times for access to diagnostic catheterization and revascularization in patients presenting with acute coronary syndromes: for diagnostic catheterization and percutaneous coronary intervention, the target should be 24 h to 48 h for high-risk, three to five days for intermediate-risk and five to seven days for low-risk patients; for coronary artery bypass graft surgery, the target should be three to five days for high-risk, two to three weeks for intermediate-risk and six weeks for low-risk patients. All stakeholders must affirm the appropriateness of these standards and work continuously to achieve them. However, some questions remain around what are the best clinical risk markers to delineate the triage categories and the utility of clinical risk scores to assist clinicians in triaging patients for invasive therapies.

General commentary on access to cardiovascular care in Canada: universal access, but when? Treating the right patient at the right time.

In 2004, the Canadian Cardiovascular Society formed an Access to Care Working Group with a mandate to use the best science and information available to establish reasonable triage categories and safe wait times for common cardiovascular services and procedures through a series of commentaries. The present commentary is the first in the series and lays out issues regarding timely access to care that are common to all cardiovascular services and procedures. The commentary briefly describes the 'right' to timely access, wait lists as a health care system management tool, and the role of the physician as patient advocate and gatekeeper. It also provides advice to funders, administrators and providers who must monitor and manage wait times to improve access to cardiovascular care in Canada and restore the confidence of Canadians in their publicly funded health care system.

Stimulation of zif/268 gene expression by basic fibroblast growth factor in primary rat striatal cultures.

The presence of basic fibroblast growth factor (bFGF) in the basal ganglia, and its known neurotrophic activity, has created interest in its possible role as an agent to attenuate striatal neurodegeneration. However, little information is available on the mechanisms through which bFGF might exert a long-term influence on striatal function. Primary cultures of embryonic rat striatal neurones were used to ascertain whether bFGF can alter the pattern of striatal gene expression. Treatment of cultures with bFGF (500 pM) resulted in a dramatic increase in the levels of zif/268 mRNA within 45 min. This induction was attenuated by the tyrosine kinase inhibitor genistein (100 microM), but not by its inactive structural analogue genistin (100 microM). The induction of zif/268 mRNA was found to occur in non-neuronal cells, with no increase in mRNA levels being observed in neurones. A similar induction was noted for another putative transcription factor, jun B, although no induction of the related factor jun D could be detected. These results show that bFGF can induce immediate-early gene expression in striatal cultures, and therefore that this may provide a mechanism, mediated by non-neuronal cells, which allows bFGF to cause a long-term change in striatal neurochemistry.

Dynamic changes in NADPH-diaphorase staining reflect activity of nitric oxide synthase: evidence for a dopaminergic regulation of striatal nitric oxide release.

In fixed tissue, neuronal NADPH-diaphorase staining results from nitric oxide synthase (NOS) activity. Neuronal NOS only synthesizes nitric oxide once activated by the binding of Ca2+/calmodulin. We show here that neuronal NADPH-diaphorase staining is also dependent on Ca2+/calmodulin, implying that only activated NOS is detected. In addition, in bovine pulmonary endothelial cells, carbachol and bradykinin dramatically and rapidly increase the intensity of NADPH-diaphorase staining. Furthermore, administration of MK801, an NMDA antagonist, decreases neuronal NADPH-diaphorase staining. This suggests that the intensity of the NADPH-diaphorase staining is related to the level of enzyme activation at the moment of tissue fixation. The potential of exploiting this observation to detect cellular activation of NOS is illustrated by the observations that the intensity of NADPH-diaphorase staining in rat striatal neurones is decreased following systemic treatment with the D1-like dopamine receptor antagonist SCH23390, and increased by the D2-like antagonist eticlopride. These results therefore provide strong evidence that the NADPH-diaphorase reaction can be used to monitor NOS activity at a cellular level of resolution, and reveal a dopaminergic regulation of NOS activity in the striatum mediated by D1-like and D2-like dopamine receptors.

Induction of c-fos and zif/268 gene expression in rat striatal neurons, following stimulation of D1-like dopamine receptors, involves protein kinase A and protein kinase C.

Changes in the level of dopaminergic activity in the rat striatum lead to the induction of a number of immediate-early genes, including c-fos and zif/268. These immediate-early genes are thought in turn to alter the rate of transcription of downstream genes. There is evidence that the dopaminergic activation of the c-fos and zif/268 genes in the striatum in vivo is linked to stimulation of D1-like dopamine receptors. We have used primary cultures of embryonic rat striatal neurons to identify the intracellular pathways involved in this response. Dopamine (10 nM-5 microM) caused a marked increase in the levels of c-fos mRNA and zif/268 mRNA in cultured striatal neurons, an effect that was reproduced by the D1-like dopamine receptor agonist SKF38393 (10 nM-5 microM). These actions were attenuated by the D1-like antagonist SCH23390 (1 microM) but not by the D2-like antagonist eticlopride (1 microM). The D2-like agonist quinpirole did not increase zif/268 mRNA above basal levels at concentrations up to 5 microM, but caused a slight increase in the levels of c-fos mRNA. The stimulation of c-fos mRNA levels caused by 1 microM SKF38393 was reduced by 45% following pretreatment with the selective protein kinase A inhibitor KT5720, and by 87% following pretreatment with the selective protein kinase C inhibitor calphostin C. The stimulation of zif/268 mRNA levels caused by 1 microM SKF38393 was reduced by 90% following pretreatment with KT5720, but was not significantly affected by pretreatment with calphostin C. In addition, the actions of SKF38393 to stimulate the expression of both immediate-early genes were attenuated by coadministration of quinpirole. These results suggest that SKF38393 acts on striatal neurons to stimulate c-fos expression predominantly through protein kinase C, but also partially through protein kinase A. Conversely, SKF38393 induces zif/268 expression through protein kinase A. The ability of quinpirole to antagonize the actions of SKF38393 on cultured neurons is consistent with the presence of both D1-like receptors on the same neuronal population.

Basic fibroblast growth factor induces c-fos expression in primary cultures of rat striatum.

Basic fibroblast growth factor (bFGF) is present in the rat striatum in vivo, where evidence suggests it may have a long-term trophic role in supporting the survival of striatal neurones. To examine the possibility that these effects of bFGF might be mediated by induction of neuronal gene expression, we have investigated the ability of bFGF to stimulate expression of the immediate-early gene c-fos in primary cultures of embryonic rat striatum. The basal levels of c-fos mRNA were low in both neurones and glia in culture. Application of 500 pM bFGF resulted, within 45 min, in a 11-fold increase in the c-fos hybridisation signal in the non-neuronal cells. No significant induction of c-fos mRNA was detected in the striatal neurones at this time. The induction in non-neuronal cells was blocked by the tyrosine kinase inhibitor genistein (100 microM), but not by its inactive structural analogue genistin (100 microM). These results represent a novel mechanism whereby bFGF can exert prolonged effects on striatal function, and indicate that the increases in striatal c-fos gene expression induced by bFGF occur primarily in non-neuronal cells.

Neuronal expression of protease-nexin 1 mRNA in rat brain.

Protease-nexin 1 (PN1), also known as glia-derived nexin, is a protease inhibitor secreted by cultured fibroblasts and glioma cells, with postulated roles in regeneration and the regulation of neurite outgrowth. In this study we have localised the sites of PN1 gene expression in rat brain using in situ hybridisation. As expected, cultured cortical astrocytes contained relatively high levels of PN1 mRNA. However, the mRNA localisation in rat brain suggested that the primary sites of synthesis in the CNS are neuronal. Relatively high levels of PN1 mRNA were found in the olfactory nerve layer of the olfactory bulb, in layer V of the cerebral cortex, in magnocellular neurones of the basal forebrain, and in scattered neurones of the striatum. The results show that PN1 gene expression occurs in discrete populations of neurones in the brain, and suggest that these neurones may therefore play a role in the local regulation of neurite outgrowth.

Recurrent seizure diagnosed by the insertable loop recorder.

INTRODUCTION: The Insertable Loop Recorder (ILR) has emerged as an important new tool in the diagnostic armamentarium for patients with syncope. METHODS AND RESULTS: A case report illustrates how the ILR unexpectedly led to the diagnosis of seizure as the explanation for a man's recurrent, but infrequent episodes of sudden loss of consciousness. CONCLUSIONS: This case raises the possibility that the development of implantable recording devices which monitor physiologic parameters other than cardiac rhythm (eg. brain, nerve or muscle activity) may provide the long-term monitoring capability needed to improve the diagnostic yield for conditions, such as seizures, which occur infrequently.

Correlation of waiting time with adverse events in patients admitted for nonelective permanent pacemaker implantation.

OBJECTIVE: To determine the effect of a dedicated permanent pacemaker implantation procedure room on waiting time and waiting time-related morbidity. DESIGN: Retrospective chart review. SETTING: Two tertiary care teaching hospitals in southern Ontario; one with a dedicated procedure room (centre B) and one without (centre A). PATIENTS: Two hundred and fourteen consecutive patients who required permanent pacing urgently or emergently. METHODS: Charts were examined retrospectively at centre A (131 patients) and centre B (83 patients) to determine the waiting time for and the number of preoperative adverse events in nonelective permanent pacemaker implantation. RESULTS: Patients in centre A waited a mean of 4.5 +/- 3.0 days while patients in centre B waited a mean of 1.9 +/- 1.6 days (P = 0.0001). Centre A patients experienced a total of 57 adverse events that were likely or possibly related to the waiting period, while patients at centre B experienced eight such events (P < 0.0001). Thirty-three per cent of the centre A patients experienced at least one adverse event, while 8% of centre B patients experienced at least one adverse event (P < 0.00001). Of the centre A patients who waited for more than six days (26 patients), 58% had at least one adverse event, compared with 26% of those who waited less than six days (105 patients, P = 0.0009). CONCLUSIONS: Delays in implanting nonelective permanent pacemakers are strongly associated with an increase in adverse events. Measures to shorten the waiting time are likely to result in a reduction in morbidity in conjunction with a beneficial impact on health care resource utilization.

A cost effective approach to the investigation of syncope: relative merit of different diagnostic strategies.

OBJECTIVE: To compare the cost effectiveness of a conventional diagnostic work-up with that of several different diagnostic cascades for the investigation of undifferentiated syncope. DESIGN: A MEDLINE search established a weighted estimate of diagnostic yield for several diagnostic investigations. 'High-end' and 'low-end' cost estimates were calculated for these investigations based on figures from four representative Canadian tertiary care centres in four different provinces. Several diagnostic models were applied to a hypothetical cohort of 100 patients with undifferentiated syncope. RESULTS: The conventional diagnostic cascade resulted in a diagnosis in 85% of patients, at a cost per diagnosis of $467 to $959. The optimal model increased the diagnostic yield to 98.9%, at a cost of $460 to $1043 per diagnosed patient. CONCLUSION: A combination of new technology and selective use of investigations has the potential to raise diagnostic yield without appreciably increasing cost per diagnosis.

Impact of a mandatory physician reporting system for cardiac patients potentially unfit to drive.

CONTEXT: Sudden cardiac incapacitation of a driver may lead to the death or serious injury of passengers or bystanders. This has raised public safety concerns and has led to the creation of legislation to protect the public. Some jurisdictions in Canada and the United States have introduced mandatory physician reporting of patients who may be unfit to drive for medical reasons. The impact on motor vehicle accident (MVA)-related morbidity and mortality of mandatory physician reporting for at-risk cardiac patients is unknown. OBJECTIVE: To determine the impact of mandatory physician reporting legislation (for cardiac patients) in Ontario (population 10.3 million) on MVA-related morbidity and mortality. DATA SOURCES: Reporting data were obtained from the Ontario Ministry of Transportation. Incidence and prevalence data were taken from Ontario Ministry of Health sources and from the literature (MEDLINE). Data for modelling were taken from the literature (MEDLINE) and from the Canadian Cardiovascular Society's Consensus Conference document on cardiac illness and fitness to drive. DATA EXTRACTION: Licence suspension data (correlated with medical illness) were taken directly from government documents. These were then applied to a 'risk of harm' formula used to calculate the risk posed to bystanders and passengers by the suspended patients if they had continued to drive. Canadian licence suspension guidelines were then reviewed in conjunction with cardiac disease incidence and prevalence data to arrive at the number of patients who should have been suspended. Physician compliance with the legislation was then calculated, along with the potential impact on MVA-related morbidity and mortality in the scenario of 100% physician compliance. STUDY SELECTION: All Ontario drivers who had licence suspensions in 1996 for reasons of cardiac disease were included in the analysis. DATA SYNTHESIS: Nine hundred and ninety-four licences were suspended for cardiac reasons in 1996, compared with an estimated 72,407 that should have been suspended if Canadian guidelines had been followed (1.4%). Less than one death or serious injury was avoided as a result of the legislation (from the 'risk of harm' formula). If all drivers with cardiac illness had been suspended from driving, up to 29.2 such events could potentially have been avoided. However, only 13 of 929 (1.4%) road fatalities in Ontario in 1996 were attributed to a driver with a medical illness. CONCLUSIONS: Mandatory physician reporting of patients with cardiac illness has a negligible impact on MVA-related morbidity and mortality.

Phenotypic characterisation of rat striatal neurones in primary culture.

The aim of this study was to determine to what extent the neuronal phenotypes present in primary cultures of rat striatal neurones correspond to those present in vivo. A large percentage of cultured striatal neurones contained relatively high levels of proenkephalin mRNA. In addition, a high level of expression was found for the prosomatostatin mRNA. Protachykinin mRNA and proneuropeptide Y mRNA were also expressed, but at a comparatively low level. No prodynorphin mRNA could be detected. Considerable numbers of neurones were also found to express NADPH-diaphorase activity, while a smaller number of neurones were positive for acetylcholinesterase. The NADPH-diaphorase and the acetylcholinesterase could be detected both in cell bodies, and in neuronal processes contacting groups of neighbouring neurones. Since nitric oxide does not require synaptic specialisations to exert its intercellular actions, this provides strong evidence that NADPH-positive neurones communicate with other cells in primary culture. These observations demonstrate that when striatal neurones are grown in primary culture, a range of neurochemical phenotypes are present which correspond closely to those present in the mature striatum in vivo. Together with the evidence for cell-cell interactions, this suggests that primary striatal cultures will provide a suitable model to study the molecular mechanisms controlling striatal function.

Canadian Cardiovascular Society commentary on implantable cardioverter defibrillators in Canada: waiting times and access to care issues.

The Canadian Cardiovascular Society is the national professional society for cardiovascular specialists and researchers in Canada. In the spring of 2004, the Canadian Cardiovascular Society Council formed an Access to Care Working Group in an effort to use the best science and information to establish reasonable triage categories and safe wait times for access to common cardiovascular services and procedures. The Working Group has elected to publish a series of commentaries to initiate a structured national discussion on this very important issue. Access to treatment with implantable cardioverter defibrillators is the subject of the present commentary. The prevalence pool of potentially eligible patients is discussed, along with access barriers, regional disparities and waiting times. A maximum recommended waiting time is proposed and the framework for a solution-oriented approach is presented.

Respectable identities: New Zealand nineteenth-century "new women" - on bicycles!

For nineteenth-century New Zealand middle-class women, cycling elicited significant anxieties about femininity. Critics ultimately feared that women would become masculine in both their appearance and their conduct. The masculinization of women was neatly embodied in the 'New Woman' who, in contrast to the conventional image of women, heralded a new feminine identity: physically and politically active, and prominent in public. The ideology of the New Woman arose in the context of widespread social change for Western women throughout the nineteenth century, after decades of agitation for improved access to education, employment, political representation, and equal legal rights with men. In this article, it is argued that middle-class female cyclists tried to reconcile the ideology of the New Woman with conventional beliefs about femininity to create an alternative, yet still respectable, identity in order to convince their critics that despite riding the bicycle, they were still feminine.