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Many payment for ecosystem services (PES) programs, such as the Slope Land Conversion Program (SLCP), are passive and require full participation by impacted households. In contrast, this study considers the alternative of "active and incomplete" participation in PES programs, in which participants are not obliged to contract their own land, and have the right to select into the program or not. This type of program has been popular over the last decade in China; however, there have been few studies on the characteristics of willingness to participate and implementation. As such, this paper uses the Choice Experiment (CE) method to explore ways for inducing effective program participation, by analyzing the effects of different regime attributes. The case study used to analyze participation utility was the Jing-Ji Afforestation Program for Ecological and Water Protection (JAPEWP), a typical active-participation forestry PES program, and a key source of water near Beijing in the Miyun Reservoir Catchment (MRC). Analyzing rural household survey data indicated that the program faces a variety of challenges, including long-term maintenance, implementation performance, cost-effectiveness, and monitoring approaches. There are also challenges with one-size-fits-all payment strategies, due to ineffective program participation or imperfect implementation regimes. In response, this study proposes several policies, including providing secure and complete land tenure to the participants, creating more local off-farm employment opportunities, designing performance-based monitoring systems that are integrated with financial incentives, applying differentiated payment strategies, providing capacity building to support forestation activities, and establishing a comprehensive implementation regime that would address these challenges. These policy conclusions provide valuable lessons for other active-participation PES programs as well., Competing Interests: The authors have declared that no competing interests exist.

Background: The protective effect of beta-blockers in patients with inherited Long-QT syndrome is well established. Recent reports have suggested that beta-blockers are not equally effective in Long-QT (LQT). Bisoprolol is an attractive candidate for use in LQT because of its cardioselective properties and favorable side-effect profile., Methods: We performed a retrospective cohort study of 114 consecutive patients with gene-positive Long-QT syndrome type 1 (LQT1) or Long-QT syndrome type 2 (LQT2) treated with bisoprolol, nadolol or atenolol with a total of 580 person-years of follow-up. Electrocardiogram (ECG) parameters and cardiac events during follow-up were compared. In addition, exercise treadmill testing was performed in bisoprolol-treated patients., Results: Fifty-nine patients were treated with bisoprolol, 39 with atenolol and 16 with nadolol. Overall, 59 % were females and 62 % had LQT1. Baseline heart rate and corrected QT (QTc) interval were similar between the groups. QTc shortening was observed in individuals on bisoprolol (ΔQTc -5 ± 31 ms; p = 0.049) and nadolol (ΔQTc -13 ± 16 ms; p = 0.02) but not on atenolol (ΔQTc +9 ± 24 ms; p = 0.16). Median follow-up was similar for bisoprolol and nadolol (3 years), but longer for atenolol (6 years; p = 0.03); one cardiac event occurred in the bisoprolol group (1.7 %) and two events occurred in the atenolol group (5.1 %; p = 0.45), whereas none occurred in nadolol-treated patients. Beta-blocker efficacy was not affected by the underlying genotype. The antiadrenergic effect of bisoprolol correlated with the reduction of peak heart rates at exercise testing., Conclusions: Bisoprolol treatment results in QTc shortening in gene-positive LQT1 and LQT2 patients and is well tolerated during long-term administration. The equivalence of bisoprolol for protection from ventricular arrhythmia in LQT patients compared to established beta-blockers remains unknown. Further large-scale studies are required.

Background: The Cardiac Arrest Survivors with Preserved Ejection Fraction Registry (CASPER) enrolls patients with apparently unexplained cardiac arrest and no evident cardiac disease to identify the pathogenesis of cardiac arrest through systematic clinical testing. Exercise testing, drug provocation, advanced cardiac imaging, and genetic testing may be useful when a cause is not apparent., Methods and Results: The first 200 survivors of unexplained cardiac arrest from 14 centers across Canada were evaluated to determine the results of investigation and follow-up (age, 48.6±14.7 years, 41% female). Patients were free of evidence of coronary artery disease, left ventricular dysfunction, or evident repolarization syndromes. Advanced testing determined a diagnosis in 34% of patients at baseline, with a diagnosis emerging during follow-up in 7% of patients. Of those who were diagnosed, 28 (35%) had an underlying structural condition and 53 (65%) had a primary electric disease. During a mean follow-up of 3.15±2.34 years, 23% of patients had either a shock or an appropriate antitachycardia pacing from their implantable cardioverter defibrillator, or both. The implantable cardioverter defibrillator appropriate intervention rate was 8.4% at 1 year and 18.1% at 3 years, with no clear difference between diagnosed and undiagnosed subjects, or between those diagnosed with a primary electric versus structural pathogenesis., Conclusions: Obtaining a diagnosis in previously unexplained cardiac arrest patients requires systematic clinical testing and regular follow-up to unmask the cause. Nearly half of apparently unexplained cardiac arrest patients ultimately received a diagnosis, allowing for improved treatment and family screening. A substantial proportion of patients received appropriate implantable cardioverter defibrillator therapy during medium-term follow-up., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00292032., (© 2016 American Heart Association, Inc.)

Introduction: Medtronic's Lead Integrity Alert (LIA) software algorithm is useful for detecting abnormal parameters across various ICD-lead families. However, its utility in the assessment of the Biotronik Linox™ family of high-voltage (HV) leads is unknown., Methods: We conducted a retrospective cohort study to assess the performance of the LIA algorithm to detect abnormalities and lead failure in Linox ICD-leads. All LIA-enabled Medtronic devices connected to an active Linox lead were included. The alerts were adjudicated by 2 blinded electrophysiologists and correlated with clinical data., Results: Between 2008 and 2012, data from 208 patients with 564 patient-years of follow-up were available for analysis. The median follow-up duration was 32 (IQR 21-41 months). Twenty-one LIA triggers were noted in 20 different patients. The median delay until a positive LIA was 32 months (IQR 21-41 months) postimplant with a 5-year lead survival free from LIA of 76%. Ninety-five percent (19/20) LIA alerts were true lead failures. The most common LIA triggers were short V-V intervals (85%) and nonsustained ventricular tachycardia (85%). Abrupt changes of the ICD-lead impedance occurred in 5/20 triggers. Inappropriate ICD-shocks were strongly associated with a positive LIA (30% vs. 7.4%; P = 0.006). Of the explanted Linox leads 53% had visible abnormalities. The sensitivity, specificity, and positive predictive value for lead failure in the presence of a LIA trigger were 87%, 99.5%, and 95.2%, respectively., Conclusions: A positive LIA trigger in Biotronik Linox ICD-leads is highly predictive of lead failure. LIA is useful in ongoing surveillance of lead performance., (© 2015 Wiley Periodicals, Inc.)

Cardiac implantable electronic devices (CIEDs) have dramatically improved clinical outcomes in patients with heart disease, and the number of CIED-related procedures being performed continues to grow. Unfortunately, the rate of device-related infection (DRI) is increasing disproportionately to the rate of implantation, with DRI rates of >2% in many series. This increase in DRI is a consequence of the increased number of patients with a higher burden of comorbidities, who are more susceptible to infection and are undergoing more complex device procedures. Identification of high-risk patients is an important component of procedural planning, and targeted therapy and surveillance may be beneficial in certain groups. An understanding of the pathophysiology of DRI has facilitated more effective and widespread use of prophylactic antibiotics; however, current guidelines for antibiotic prophylaxis are based on a relatively small evidence base. Clinical equipoise remains regarding the optimal prophylactic regimen, and we are continuing to learn how best to manage these patients. In this review, we discuss the epidemiology and pathophysiology of DRI and its clinical presentation, the risk factors for DRI, and the existing and emerging evidence supporting strategies to prevent DRI., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Cardiac resynchronization therapy (CRT) is underused. Recent guidelines have expanded indications for CRT to include less severe symptoms but now favor left bundle branch block morphology in patients with moderate QRS prolongation. The prevalence of CRT eligibility according to historical and current guidelines is uncertain. The aim of this review was to identify and synthesize all existing published research reporting the prevalence of CRT eligibility. A systematic review of electronic databases including MEDLINE, Embase, and the Cochrane Library was performed. The primary outcome was the proportion of patients eligible for CRT according to historical and current criteria. Secondary outcomes included the individual components of eligibility (the ejection fraction, symptoms, and QRS duration and morphology). Eligibility estimates were pooled using random-effects models because of marked heterogeneity in between-study variance. Thirty studies were identified. No study used current guideline criteria. On the basis of historical criteria, 11 ± 3% of ambulatory and 9 ± 3% of hospitalized patients are eligible for CRT. However, New York Heart Association class II in current guidelines is at least as frequent as New York Heart Association III or IV. Approximately 1/3 of patients have QRS prolongation, 2/3 of whom have left bundle branch block. Only a few patients have non-left bundle branch block with QRS duration <150 ms. Medical contraindication or ineligibility was rarely assessed. In conclusion, current estimates of need are outdated. Inclusion of milder symptoms potentially doubles the eligible population. Studies in unselected cohorts are needed to accurately define the individual components of eligibility, together with the prevalence and reasons for ineligibility., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: HIV-infected patients on antiretroviral therapy frequently develop dyslipidemias and, despite therapy with potent lipid-lowering agents, a high percentage does not achieve guideline recommended lipid targets. In this study, we examined the efficacy of combination treatment with a statin and the cholesterol transport blocker, ezetimibe, vs. monotherapy with a statin in HIV-infected patients not achieving lipid goals., Methods: This was a 12-week, prospective, randomized, open-label clinical trial. Patients were eligible if they had an apolipoprotein B (apoB) >0.80 g/L despite therapy with rosuvastatin 10 mg daily for a minimum of 12 weeks. Patients were randomized to take ezetimibe 10 mg/rosuvastatin 10 mg or rosuvastatin 20 mg for 12 weeks. Percentage and absolute change in apoB (primary outcome), low-density lipoprotein cholesterol (LDL-C), total cholesterol (TC), triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), non-HDL-C, apoliporpotein A1 (apoA1), apoB/apoA1, TC/HDL-C, atherogenic index of plasma (API), and high-sensitivity C-reactive protein (hsCRP) were compared. Changes in safety parameters (such as AST, ALT, CK) and clinical symptoms were also assessed., Results: Forty-three patients (23 on ezetimibe 10 mg/rosuvastatin 10 mg and 20 on rosuvastatin 20 mg) completed the trial. Baseline characteristics did not differ between the groups. Significant improvements in apoB were seen with both ezetimibe plus rosuvastatin (mean of -0.17 g/L, p < 0.001) and rosuvastatin 20 mg (mean of -0.13 g/L, p = 0.03) treatment groups, but did not differ between groups (p = 0.53). Significant between-group differences were observed for mean TC (-1.01 mmol/L vs. -0.50 mmol/L, p = 0.03), TG (-0.62 mmol/L vs -0.17 mmol/L, p = 0.03), and non-HDL-C (-0.97 mmol/L vs. -0.53 mmol/L, p = 0.03) all in favour of the ezetimibe plus rosuvastatin group. Two patients, both in the rosuvastatin 20 mg group, experienced mild myalgias; neither discontinued the study., Conclusions: The addition of ezetimibe to rosuvastatin appears to be safe in patients with HIV. Furthermore, the combination of ezetimibe and rosuvastatin improved TG, AIP and non-HDL cholesterol levels more than a dose increase in rosuvastatin in patients with HIV-associated dyslipidemia.

Background: Social health is a dimension of quality of life, and refers to people's involvement in, and satisfaction with social roles, responsibilities, and activities. The implantable cardioverter-defibrillator is associated with changes in overall quality of life, but little is known about sex differences in individual trajectories of change in social health., Methods and Results: We prospectively measured changes in 3 subscales of the SF-36v2 generic health questionnaire (role physical, role emotional, and social functioning), 2 Patient-Reported Outcomes Measurement Information System short forms (satisfaction with participation in social roles and satisfaction with participation in discretionary social activities), and the Florida Patient Acceptance Survey before and at 1, 2, and 6 months after implantation. Individual growth models of temporal change were estimated. The scores of the 6 indicators improved with time. The unconditional model demonstrated significant (fixed effects: P<0.05; covariance parameters: P<0.10) residual variability in the individual trajectories. In the conditional model, men and women differed significantly in their rates of change in the scores of 3 of the 6 measures. Although men's mean scores exceeded women's mean scores on all indicators at baseline (range of relative mean difference: 11.0% to 17.8%), the rate of women's change resulted in a reversal in relative standing at 6 months after implantation, with the mean scores of women exceeding the men's by 4.5% to 5.6%., Conclusions: Men and women differed in their trajectories of change in social health, both in terms of their starting points (ie, baseline scores) and their rates of change., (© 2015 American Heart Association, Inc.)

Introduction: The Linox and Durata implantable cardioverter defibrillator (ICD) leads were introduced to British Columbia (BC) in 2008. We determined their performance and the potential risk factors for lead failure in a large population-based patient registry., Methods and Results: We used the BC Cardiac Registry, a mandatory Governmental database of ICD implants, to identify all recipients of Linox and Durata leads in BC between October 2008 and April 2012, and those subsequently undergoing reoperation. Lead failure was defined as recurrent nonphysiological high-rate sensing unrelated to external electromagnetic interference or T-wave oversensing; a sudden rise in impedance unrelated to perforation or lead dislodgement; or abnormal lead parameters with definite evidence of lead fracture or insulation failure. We determined the estimated cumulative lead survival by the Kaplan-Meier method, and the risk factors for lead failure in a proportional hazards model. Over a median of 39 (27-50) months, the Linox failed more frequently than the Durata (16/477 [3.4%] vs. 4/838 [0.4%]; P < 0.001), and had a significantly lower estimated cumulative survival (91.6 [80.6-96.5]% vs. 99.4 [98.4-99.8]% at 5 years; P < 0.0001). Linox failure was characterized by high-rate nonphysiological sensing (11 cases), and/or a sudden impedance rise (7 cases). Insulation failure was clearly confirmed in 6 cases of Linox failure. Female sex was a significant risk factor for Linox failure (adjusted HR = 2.1[1.3-3.4]; P = 0.004)., Conclusions: This multicenter registry indicates a high rate of Linox lead failure, particularly in female patients. Ongoing surveillance of the Linox ICD lead performance is recommended., (© 2014 Wiley Periodicals, Inc.)

Aims: Beta-blockers are the standard of care for the treatment of long QT syndrome (LQTS), and have been shown to reduce recurrent syncope and mortality in patients with type 1 LQTS (LQT1). Although beta-blockers have minimal effect on the resting corrected QT interval, their effect on the dynamics of the non-corrected QT interval is unknown, and may provide insight into their protective effects., Methods and Results: Twenty-three patients from eight families with genetically distinct mutations for LQT1 performed exercise stress testing before and after beta-blockade. One hundred and fifty-two QT, QTc, and Tpeak-Tend intervals were measured before starting beta-blockers and compared with those at matched identical cycle lengths following beta-blockade. Beta-blockers demonstrated heart-rate-dependent effects on the QT and QTc intervals. In the slowest heart rate tertile (<90 b.p.m.), beta-blockade increased the QT and QTc intervals (QT: 405 vs. 409 ms; P = 0.06; QTc: 459 vs. 464 ms; P = 0.06). In the fastest heart rate tertile (>100 b.p.m.), the use of beta-blocker was associated with a reduction in both the QT and QTc intervals (QT: 367 vs. 358 ms; P < 0.0001; QTc: 500 vs. 486 ms; P < 0.0001). The Tpeak-Tend interval showed minimal change at slower heart rates (<90 b.p.m.) (93 vs. 87 ms; P = 0.09) and at faster heart rates (>100 b.p.m.) (87 vs. 84 ms; P = NS) following beta-blockade., Conclusion: Beta-blockers have heart-rate-dependent effects on the QT and QTc intervals in LQTS. They appear to increase the QT and QTc intervals at slower heart rates and shorten them at faster heart rates during exercise., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Syncope is common, has a high recurrence rate and carries a risk of morbidity and, dependent on the cause, mortality. Although the majority of patients with syncope have a benign prognosis, syncope as a result of cardiomyopathy or channelopathy carries a poor prognosis. In addition, the identification of these disorders allows for the institution of treatments, which are effective at reducing the risk of both syncope and mortality. It is for these reasons that the identification of a cardiomyopathy or channelopathy in patients with syncope is crucial. This review article will describe the characteristics of common cardiomyopathies and channelopathies and their investigation., (Copyright © 2014 Elsevier B.V. All rights reserved.)

Objective: The Epiducer lead delivery system is a novel lead delivery device that can be used to percutaneously implant S-Series paddle leads (St. Jude Medical, Plano, TX, USA) as well as multiple percutaneous leads obviating the need for laminectomy and/or multiple needle sticks, respectively. This study evaluates the safety and usage of the Epiducer lead delivery system., Methods: An Institutional Review Board-approved observational data collection study was conducted to evaluate usage patterns of the Epiducer system. In addition to the number and frequency of different lead configurations, the following procedural aspects of the surgery were recorded during the evaluation: angle of entry, distance from entry to final lead placement, and physician feedback. Descriptive statistics on adverse events, procedural aspects, and patient outcomes were compiled., Results: Data were collected from 163 patients across 25 investigational sites. Physicians successfully implanted patients using the Epiducer during 89% of the procedures. Seven possible lead configurations were implanted. There were 96% and 92% of physicians "satisfied" or "very satisfied" with accessing the epidural space and placing multiple leads with the Epiducer delivery system, respectfully. Eighty-nine percent of physicians were "satisfied" or "very satisfied" with implanting an S-Series paddle lead using the Epiducer delivery system. Ninety-five percent of physicians were "satisfied" or "very satisfied" with the Epiducer delivery system overall. Ten patients (6%) experienced adverse events., Conclusion: Results suggest that the Epiducer delivery system allows for the safe and successful percutaneous implantation of paddle leads and/or multiple lead configurations. Furthermore, physicians are satisfied with the Epiducer delivery system., (© 2014 International Neuromodulation Society.)

Atrial fibrillation (AF) is the most common sustained arrhythmia seen in clinical practice, affecting approximately 1% of the overall population. While rarely life-threatening, AF is almost universally associated with increased morbidity and mortality, predominantly through an increased risk of thromboembolic events, left ventricular dysfunction, as well as significant impairments in functional capacity and health-related quality of life (HRQOL).[1-8] Improvement in HRQOL, with a secondary reduction of disability and health-care resource utilization, is one of the major therapeutic goals in the management of AF.

At last there is now more than 1 oral anticoagulant (OAC) available for stroke prevention in atrial fibrillation. Though more choice is a good thing, it does mandate knowing which drug is the most appropriate in a given clinical situation. Three novel OACs--dabigatran, rivaroxaban, and apixaban--are approved for use in atrial fibrillation in Canada. They have each been evaluated in large, randomized controlled trials where they have been shown to be noninferior, or in some cases superior, to warfarin (Coumadin). Prescription coverage for these drugs is increasingly available through third party and government drug plans. The major enhancements of the novel OACs relate to their rapid, consistent anticoagulant effect at fixed dosing and the lack of need for monitoring of anticoagulant effect. Nonetheless, their use is not foolproof and practitioners must be familiar with their limitations. On balance, we favour the use of novel OACs over warfarin in patients who are anticoagulant-naive, given their increased ease of use. However, we advocate switching from warfarin only if international normalized ratio control has been poor or if frequent monitoring is problematic., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: The St. Jude Medical Riata family of implantable cardioverter-defibrillator (ICD) leads has demonstrated a high rate of externalized conductors and electrical failure., Objective: Given similar design elements of Durata to Riata, the purpose of this study was to assess the rates of failure of the Riata ST Optim and Durata lead families in Canada., Methods: All Canadian ICD-implanting centers were invited to submit follow-up information on all Optim-coated ICD leads implanted. Electrical failure was defined as a rapid change in impedance or pacing capture threshold leading to lead revision, or oversensing due to noise. Externalized conductors were defined as appearance of conductor wires outside the lead body. Systematic fluoroscopic screening for externalized conductors was not performed., Results: As of December 1, 2012, 15 of 25 centers provided data on 3981 leads (44% of those sold in Canada during the same timeframe): 3477 Durata and 504 Riata ST Optim leads. The most common model numbers were 7122 (1516 leads [38%]), 7121 (707 leads [18%]), and 7120 (622 leads [16%]). Mean follow-up duration from implant to December 1, 2012, was 4.47 ± 0.48 years for Riata ST Optim leads and 2.00 ± 1.10 years for Durata leads. The annual rate of lead failure was 0.27% per year for Riata ST Optim leads and 0.24% per year for Durata leads. No instances of externalized conductors were identified in the failed leads. No deaths were attributed to lead failure; however, 2 patients experienced inappropriate shocks due to lead failure., Conclusion: The overall electrical failure rates of the Riata ST Optim and Durata leads appear to be low, and no instances of externalized conductors were observed., (© 2013 Heart Rhythm Society. All rights reserved.)

Background: There is a relative paucity of data linking inappropriate implantable cardioverter-defibrillator (ICD) shocks to adverse clinical outcomes., Objective: To examine the association between inappropriate ICD shocks and mortality or heart transplantation in a large population cohort., Design, Setting, Patients: A cohort study which included all subjects who underwent ICD implantation between 1998 and 2008 and were followed up at our institution., Main Outcome Measures: Multivariable Cox regression analyses were conducted to investigate the effect of inappropriate shocks on the risk of death and heart transplantation. Appropriate and inappropriate ICD therapies were modelled as time-dependent covariates., Results: A total of 1698 patients were included. During a median follow-up of 30 months, there were 246 (14.5%) deaths and 42 (2.5%) heart transplants. The incidence of inappropriate shocks was 10% at 1 year and 14% at 2 years. In the adjusted model, inappropriate shocks were not associated with death or transplantation (HR=0.97, 95% CI 0.70 to 1.36, p value=0.873). In contrast, appropriate shocks were associated with adverse outcomes (HR=3.11, 95% CI 2.41 to 4.02, p value<0.001). The lack of association between inappropriate shocks and outcomes persisted for those with severely impaired left ventricular function (ejection fraction <30%) and for those receiving multiple inappropriate treatments., Conclusions: In this study, we observed no association between inappropriate ICD shocks and increased mortality or heart transplantation, even among those with severely impaired cardiac function. These findings question whether inappropriate ICD shocks lead to adverse outcomes.

We report a case in which a patient with dilated cardiomyopathy presented with syncope, terminated by a shock from his implantable cardioverter defibrillator. However, subsequent interrogation of the device revealed no tachycardia detection or treatment parameters. The mystifying details of the case were unravelled by remote consultation with the staff electrophysiologist and the use of smart phone-transmitted live images. This case highlights the use of mobile phone-facilitated video conferencing in urgent management of intracardiac device therapy. Judicious use of this technology has the potential to deliver effective and cost-effective solutions for many device-related emergencies in patients at remote settings., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Background: Epidemiological studies of pediatric inflammatory bowel diseases (IBD) are needed to generate etiological hypotheses and inform public policy; yet, rigorous population-based studies of the incidence and natural history of Crohn's disease (CD) and ulcerative colitis (UC) in the United States are limited., Methods: We developed a field-tested prospective system for identifying all new cases of IBD among Wisconsin children over an 8-year period (2000-2007). Subsequently, at the end of the study period, we retrospectively reconfirmed each case and characterized the clinical course of this incident cohort., Results: The annual incidence of IBD among Wisconsin children was 9.5 per 100,000 (6.6 per 100,000 for CD and 2.4 per 100,000 for UC). Approximately 19% of incident cases occurred in the first decade of life. Over the 8-year study period, the incidence of both CD and UC remained relatively stable. Additionally, (1) childhood IBD affected all racial groups equally, (2) over a follow-up of 4 years, 17% of patients with CD and 13% of patients with patients with UC required surgery, and (3) 85% and 40% of children with CD were treated with immunosuppressives and biologics, respectively, compared with 62% and 30% of patients with UC., Conclusions: As in other North American populations, these data confirm a high incidence of pediatric-onset IBD. Importantly, in this Midwestern U.S. population, the incidence of CD and UC seems to be relatively stable over the last decade. The proportions of children requiring surgery and undergoing treatment with immunosuppressive and biological medications underscore the burden of these conditions.

Unexplained cardiac arrest is defined as a cardiac arrest in the absence of coronary artery disease and overt structural heart disease, present in 5%-10% of cardiac arrest survivors. A genetic contribution to cardiac arrest is more common in this population, most commonly attributed to an inherited ion channel abnormality leading to familial syncope and sudden death. The common causes are Long QT and Brugada syndrome, catecholaminergic ventricular tachycardia, idiopathic ventricular fibrillation, and early repolarization syndrome. Latent structural causes include inherited cardiomyopathy such as arrhythmogenic right ventricular cardiomyopathy. We review these causes in detail and a structured approach to the investigation of these patients, which provides a diagnosis in approximately half of these patients. This allows for the initiation of disease-specific treatments and enables family screening., (Copyright © 2013 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Anemia of chronic disease (ACD) and iron deficiency anemia (IDA) are the most prevalent forms of anemia and often occur concurrently. Standard tests of iron status used in differential diagnosis are affected by inflammation, hindering clinical interpretation. In contrast, soluble transferrin receptor (sTfR) indicates iron deficiency and is unaffected by inflammation. Objectives of this prospective multicenter clinical trial were to evaluate and compare the diagnostic accuracy of sTfR and the sTfR/log ferritin index (sTfR Index) for differential diagnosis using the automated Access(®) sTfR assay (Beckman Coulter) and sTfR Index. We consecutively enrolled 145 anemic patients with common disorders associated with IDA and ACD. Subjects with IDA or ACD + IDA had significantly higher sTfR and sTfR Index values than subjects with ACD (P < 0.0001). ROC curves produced the following cutoffs for sTfR: 21 nmol/L (or 1.55 mg/L), and the sTfR Index: 14 (using nmol/L) (or 1.03 using mg/L). The sTfR Index was superior to sTfR (AUC 0.87 vs. 0.74, P < 0.0001). Use of all three parameters in combination more than doubled the detection of IDA, from 41% (ferritin alone) to 92% (ferritin, sTfR, sTfR Index). Use of sTfR and the sTfR Index improves detection of IDA, particularly in situations where routine markers provide equivocal results. Findings demonstrate a significant advantage in the simultaneous determination of ferritin, sTfR and sTfR Index. Obtaining a ferritin level alone may delay diagnosis of combined IDA and ACD., (Copyright © 2011 Wiley-Liss, Inc.)

Background: We describe urinary neutrophil gelatinase-associated lipocalin (uNGAL) values in association with clinical characteristics and urinary parameters in adults undergoing coronary angiography., Methods: This is an observational study of consecutive patients who underwent elective coronary angiography during a 4-month period in a large urban tertiary care hospital., Results: One hundred and thirteen patients were enrolled, and 100 had sufficient data to be included in the analyses. A large range of preprocedural uNGAL levels were observed (range 1-269 ng/mg Cr). Median preprocedural uNGAL was 8 ng/mg Cr. Age (P = 0.009), serum creatinine (P = 0.077) and albumin excretion (P = 0.009) were significant predictors of baseline uNGAL. Half the cohort demonstrated an increase and half a decrease in the absolute values of uNGAL after angiography, irrespective of preprocedural levels., Conclusions: We observed variable, but relatively low absolute levels of uNGAL prior to angiography in this 'cardiac' cohort. Only age, serum creatinine and albumin excretion could explain some of this variability. When designing studies of at-risk individuals where uNGAL may be used as a marker for acute kidney injury, this variability should be taken into account.

Background: The response to right ventricular (RV) entrainment is useful to distinguish atypical AV node reentrant tachycardia from AV reentrant tachycardia using a septal accessory pathway. Whether entrainment can differentiate between AV node reentrant tachycardia and AV reentrant tachycardia in patients with long-RP tachycardia has not been systematically validated., Methods and Results: Twenty-four patients with concealed septal accessory pathways who had an electrophysiology study between January 1, 2000, and January 1, 2010, were included (age, 38 ± 17 years; men, 17). Entrainment was performed from the RV apex pacing at cycle length 20 to 40 ms shorter than tachycardia cycle length (TCL). The mean TCL was 390 ± 80 ms, the mean AH interval during tachycardia was 151 ± 57 ms, and the mean ventriculoatrial (VA) time was 182 ± 103 ms. Twelve patients had typical accessory pathways (VA/TCL <40%), and 12 had slowly conducting accessory pathways (VA/TCL ≥ 40%). In all patients with typical accessory pathways, the postpacing interval minus the TCL (PPI-TCL) was <115 ms and the difference in the VA interval during pacing and tachycardia (StimA-VA) was <85 ms. On the other hand, in 6 of the 12 patients in the slowly conducting group, the PPI-TCL was >115 ms, and the StimA-VA was > 85 ms., Conclusions: Slowly conducting accessory pathways frequently yield RV entrainment criteria traditionally attributable to AV node reentry. Distinguishing AV node reentry from AV reentry in patients with long-RP tachycardia requires other criteria.

Background: The success of cavotricuspid (CTI) ablation depends on the achievement of bidirectional block. Previous investigators have shown that right ventricular (RV) pacing can replace proximal coronary sinus (pCS) pacing in assessing clockwise CTI conduction block., Objective: We sought to assess bidirectional conduction using antegrade (A-V) and retrograde (V-A) conduction times in the absence of coronary sinus (CS) pacing., Methods: Counterclockwise CTI conduction block was evaluated using conduction time to the QRS from 2 pacing sites (immediately lateral and further lateral to the CTI). This was compared to the conduction time to the pCS with pacing from the same 2 lateral points. This was measured prior to ablation in 7 patients and 41 patients following ablation. To evaluate clockwise CTI conduction block we measured the conduction time to the 2 lateral sites during RV pacing and pCS pacing. This was measured in 7 patients prior to ablation and 16 patients following successful ablation., Results: The abbreviated technique correctly indicated the presence or absence of bidirectional block in all patients. Furthermore, conduction times as assessed by the 2 methods correlated well both before and after creation of bidirectional block (correlation coefficients prior to ablation: clockwise direction r = 0.92, P = 0.0036; counterclockwise direction r = 0.86, P = 0.0132; after ablation: clockwise direction r = 0.82, P = 0.0001; counterclockwise direction r = 0.91, P < 0.0001)., Conclusion: Bidirectional CTI conduction block can be successfully demonstrated using A-V and V-A conduction without the need for CS pacing. Patients need, however, to have intact A-V and V-A AV nodal conduction., (© 2010 Wiley Periodicals, Inc.)

Aims: In the era of increasing implantable cardioverter defibrillator (ICD) complexity, the ICD patient alert is deemed to be an important feature in the early detection of ICD system malfunction and is either an audible or a vibratory alert. We sought to evaluate the patient's ability to detect these ICD alerts in the device clinic setting as a surrogate endpoint of clinical utility., Methods and Results: From 1 November 2006 to 31 March 2008, 563 patients with an ICD equipped with either an audible patient alert (APA, Medtronic and Guidant; n = 485) or a vibratory monitoring alert ([VMA, St Jude Medical; n = 78) had their alarm demonstrated in the quiet clinic setting. The ability to recognize the alert was analysed and then stratified by gender, age, manufacturer, type of alert, and pocket location. The average patient age was 63.3 (± 13.6) years and 82.8% of patients were male. Implantable cardioverter defibrillator manufacturers were Medtronic (n = 464), Boston Scientific (n = 21), and SJM (n = 78). The APA was heard in 86.0% of patients. This was less likely in patients who were older, male, and where the device was placed in the submuscular position. Every patient with a VMA sensed their alert., Conclusion: In the current ICD alert technology, the ability to sense the ICD alert in the device clinic appears to be higher for the VMA than for the APA. In particular, older patients and male patients are less likely to sense the APA.

Unlabelled: Genotype and Exercise in LQTS., Background: Repolarization dynamics during exercise in patients with long-QT Syndrome (LQTS) may be influenced by various factors such as a patient's genotype. We sought to systematically characterize the repolarization dynamics during exercise in patients with LQTS with a particular focus on the influence of genotype., Methods: Three groups of patients were studied on the basis of clinical status and genotype: LQT1, LQT2, and normal controls. Twenty-five age- and gender-matched patients were selected for each group. The QTc was measured during bicycle exercise testing and its dynamics were compared between the 3 groups., Results: The degree of QTc prolongation during exercise was greater in LQTS patients (LQT1 80 ± 47 ms, LQT2 64 ± 41 ms, Control 46 ± 20 ms, P = 0.02), with significant differences between LQT1 and LQT2 patients observed at heart rates ≥ 60% of the predicted maximum (P < 0.05). LQT1 patients demonstrated progressive or persistent QTc prolongation at higher heart rates, whereas LQT2 patients demonstrated maximum QTc prolongation at submaximal heart rates (50% of the predicted maximum) with subsequent QTc correction toward baseline values at higher heart rates. Importantly, these observations were consistent regardless of age, gender, or exercise type in subgroup analyses., Conclusions: Reduced repolarization reserve in LQTS is genotype and heart rate specific., (© 2010 Wiley Periodicals, Inc.)

Right ventricular failure after orthotopic heart transplantation is associated with significant mortality and morbidity. We report the use of a paracardiac microaxial pump, the Impella RD, as a bridge to recovery in a patient with right ventricular infarction after orthotopic heart transplantation.

Background: Exercise testing has shown modest utility in the ability to diagnose and genotype long QT syndrome (LQTS). Although numerous small studies have shown a genotype-specific repolarization response to exercise, the repolarization responses during recovery from exercise have received less focus., Objective: The purpose of this study was to characterize genotype-specific QT responses during recovery from exercise and to determine its potential as a diagnostic and genotyping tool., Methods: Seventy-five patients were age and sex matched into three groups (n = 25): LQT1, LQT2, and unaffected controls based on Schwartz score and genetic testing results. Each group underwent upright burst and gradual bicycle exercise testing while being monitored by 12-lead electrocardiogram., Results: LQT1 patients had significantly longer corrected QT (QTc) than LQT2 intervals during early recovery (P <.01). Control subjects showed little variation in QTc throughout the recovery period, maintaining a QTc within normal limits. Each group showed a distinct pattern of QTc adaptation during recovery. LQT1 patients began the recovery period at a QTc of 492 +/- 11 ms, after which the QTc decreased by 33 +/- 11 ms during recovery. Conversely, the LQT2 patients began recovery at its lowest mean QTc of 420 +/- 10 ms, which increased by 40 +/- 16 ms. At the end of recovery, a QTc cut-off value of 445 ms distinguished 92% of LQTS patients from unaffected controls, while a start-of-recovery QTc cut-off of 460 ms correctly identified genotype in 80% of LQT1 and 92% of LQT2 patients., Conclusions: Genotype-specific differences exist in QT recovery after exercise. These differences can help to identify LQTS patients and distinguish LQT1 from LQT2 genotypes., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Cardiac pacemakers and implantable cardioverter/defibrillators are becoming more common due to expanded indications and increasing patient survival. In addition, these device systems are being implanted in younger patients, which increases their necessity for long-term durability. Device adverse events can be seen early, during or following implantation (perforation, lead dislodgement, infection), or late (lead fraction, insulation failure or device system infection). These adverse events can, at least in part, be attributed to intrinsic device system structure. Since the initial pacemakers and implantable cardioverter/defibrillators, many modifications in both device system hardware and software have been made to enhance both their durability and function. The current era of devices appear to have made adjustments for previous inadequacies and promise to be reliable and to function well. Despite this, however, it is necessary for clinicians to be aware of possible malfunctions, their warning signs, and the appropriate course of action should these malfunctions be encountered. In this review we describe the common device system malfunctions and device system insertion complications.

Background: Patients with HIV are subject to development of HIV metabolic syndrome characterized by dyslipidemia, lipodystrophy and insulin resistance secondary to highly active antiretroviral therapy (HAART). Rosuvastatin is a highly potent HMG-CoA reductase inhibitor. Rosuvastatin is effective at lowering LDL and poses a low risk for drug-drug interaction as it does not share the same metabolic pathway as HAART drugs. This study sought to determine the efficacy of rosuvastatin on lipid parameters in HIV positive patients with HIV metabolic syndrome., Results: Mean TC decreased from 6.54 to 4.89 mmol/L (25.0% reduction, p < 0.001). Mean LDL-C decreased from 3.39 to 2.24 mmol/L (30.8% reduction, p < 0.001). Mean HDL rose from 1.04 to 1.06 mmol/L (2.0% increase, p = ns). Mean triglycerides decreased from 5.26 to 3.68 mmol/L (30.1% reduction, p < 0.001). Secondary analysis examining the effectiveness of rosuvastatin monotherapy (n = 70) vs. rosuvastatin plus fenofibrate (n = 43) showed an improvement of 21.3% in TG and a decrease of 4.1% in HDL-C in the monotherapy group. The rosuvastatin plus fenofibrate showed a greater drop in triglycerides (45.3%, p < 0.001) and an increase in HDL of 7.6% (p = 0.08)., Conclusion: This study found that rosuvastatin is effective at improving potentially atherogenic lipid parameters in HIV-positive patients. The lipid changes we observed were of a smaller magnitude compared to non-HIV subjects. Our results are further supported by a small, pilot trial examining rosuvastatin effectiveness in HIV who reported similar median changes from baseline of -21.7% (TC), -22.4% (LDL-C), -30.1% (TG) with the exception of a 28.5% median increase in HDL. In light of the results revealed by this pilot study, clinicians may want to consider a possible resistance to statin therapy when treating patients with HIV metabolic syndrome.

Thymine DNA glycosylase (TDG) excises thymine from G.T mispairs and removes a variety of damaged bases (X) with a preference for lesions in a CpG.X context. We recently reported that human TDG rapidly excises 5-halogenated uracils, exhibiting much greater activity for CpG.FU, CpG.ClU, and CpG.BrU than for CpG.T. Here we examine the effects of altering the CpG context on the excision activity for U, T, FU, ClU, and BrU. We show that the maximal activity (k(max)) for G.X substrates depends significantly on the 5' base pair. For example, k(max) decreases by 6-, 11-, and 82-fold for TpG.ClU, GpG.ClU, and ApG.ClU, respectively, as compared with CpG.ClU. For the other G.X substrates, the 5'-neighbor effects have a similar trend but vary in magnitude. The activity for G.FU, G.ClU, and G.BrU, with any 5'-flanking pair, meets and in most cases significantly exceeds the CpG.T activity. Strikingly, human TDG activity is reduced 10(2.3)-10(4.3)-fold for A.X relative to G.X pairs and reduced further for A.X pairs with a 5' pair other than C.G. The effect of altering the 5' pair and/or the opposing base (G.X versus A.X) is greater for substrates that are larger (bromodeoxyuridine, dT) or have a more stable N-glycosidic bond (such as dT). The largest CpG context effects are observed for the excision of thymine. The potential role played by human TDG in the cytotoxic effects of ClU and BrU incorporation into DNA, which can occur under inflammatory conditions and in the cytotoxicity of FU, a widely used anticancer agent, are discussed.

To determine the efficacy and safety of adding ezetimibe to maximally tolerated lipid lowering therapy in patients with HIV dyslipidemia. Retrospective analysis of lipid parameters was conducted for 33 patients with HIV who had been prescribed ezetimibe 10 mg per day. Mean total cholesterol was reduced 21% (p < 0.001). Mean LDL was reduced 35% (p < 0.001). Mean HDL increased 8% (p = 0.038). Mean triglyceride was reduced 34% (p = 0.006). Mean Apolipoprotein B100 was reduced 33% (p = 0.043). No adverse events occurred. Ezetimibe appears safe and effective in patients with HIV when added to maximally tolerated doses of lipid lowering therapy.

Initiating the DNA base excision repair pathway, DNA glycosylases find and hydrolytically excise damaged bases from DNA. While some DNA glycosylases exhibit narrow specificity, others remove multiple forms of damage. Human thymine DNA glycosylase (hTDG) cleaves thymine from mutagenic G.T mispairs, recognizes many additional lesions, and has a strong preference for nucleobases paired with guanine rather than adenine. Yet, hTDG avoids cytosine, despite the million-fold excess of normal G.C pairs over G.T mispairs. The mechanism of this remarkable and essential specificity has remained obscure. Here, we examine the possibility that hTDG specificity depends on the stability of the scissile base-sugar bond by determining the maximal activity (k(max)) against a series of nucleobases with varying leaving-group ability. We find that hTDG removes 5-fluorouracil 78-fold faster than uracil, and 5-chlorouracil, 572-fold faster than thymine, differences that can be attributed predominantly to leaving-group ability. Moreover, hTDG readily excises cytosine analogues with improved leaving ability, including 5-fluorocytosine, 5-bromocytosine, and 5-hydroxycytosine, indicating that cytosine has access to the active site. A plot of log(k(max)) versus leaving-group pK(a) reveals a Brønsted-type linear free energy relationship with a large negative slope of beta(lg) = -1.6 +/- 0.2, consistent with a highly dissociative reaction mechanism. Further, we find that the hydrophobic active site of hTDG contributes to its specificity by enhancing the inherent differences in substrate reactivity. Thus, hTDG specificity depends on N-glycosidic bond stability, and the discrimination against cytosine is due largely to its very poor leaving ability rather than its exclusion from the active site.

All-trans-retinoic acid (ATRA) is a new and effective treatment of acute promyelocytic leukemia. It has many side-effects, including the retinoic acid syndrome and Sweet's syndrome. There have been only nine cases of hypercalcemia associated with ATRA described in the literature. We discuss a case of hypercalcemia, which we believe was due to inhibition of cytochrome P450 function by voriconizole when used concomitantly with ATRA.

Objective: To define epidemiologic and clinical characteristics of newly diagnosed pediatric inflammatory bowel disease (IBD) in a large population-based model., Study Design: All pediatric gastroenterologists providing care for Wisconsin children voluntarily identified all new cases of IBD during a 2-year period. Demographic and clinical data were sent to a central registry prospectively for analysis., Results: The incidence of IBD in Wisconsin children was 7.05 per 100,000, whereas the incidence for Crohn's disease was 4.56, more than twice the rate of ulcerative colitis (2.14). An equal IBD incidence occurred among all ethnic groups, and children from sparsely and densely populated counties were equally affected. The majority (89%) of new IBD diagnoses were nonfamilial., Conclusions: This study provides novel, prospective, and comprehensive information on pediatric IBD incidence within the United States. The surprisingly high incidence of pediatric IBD, the predominance of Crohn's disease over ulcerative colitis, the low frequency of patients with a family history, the equal distribution of IBD among all racial and ethnic groups, and the lack of a modulatory effect of urbanization on IBD incidence collectively suggest that the clinical spectrum of IBD is still evolving and point to environmental factors contributing to the pathogenesis.

Redband trout (Oncorhynchus mykiss ssp.) in southeastern Oregon inhabit high-elevation streams that exhibit extreme variability in seasonal flow and diel water temperature. Given the strong influence and potential limitations exerted by temperature on fish physiology, we were interested in how acute temperature change and thermal history influenced the physiological capabilities and biochemical characteristics of these trout. To this end, we studied wild redband trout inhabiting two streams with different thermal profiles by measuring (1) critical swimming speed (U(crit)) and oxygen consumption in the field at 12 degrees and 24 degrees C; (2) biochemical indices of energy metabolism in the heart, axial white skeletal muscle, and blood; and (3) temperature preference in a laboratory thermal gradient. Further, we also examined genetic and morphological characteristics of fish from these two streams. At 12 degrees C, maximum metabolic rate (Mo2max) and metabolic power were greater in Little Blitzen redband trout as compared with those from Bridge Creek (by 37% and 32%, respectively). Conversely, Bridge Creek and Little Blitzen trout had similar values for Mo2max and metabolic power at 24 degrees C. The U(crit) of Little Blitzen trout was similar at the two temperatures (61+/-3 vs. 57+/-4 cm s(-1)). However, the U(crit) for Bridge Creek trout increased from 62+/-3 cm s(-1) to 75+/-3 cm s(-1) when water temperature was raised from 12 degrees to 24 degrees C, and the U(crit) value at 24 degrees C was significantly greater than for Little Blitzen fish. Cost of transport was lower for Bridge Creek trout at both 12 degrees and 24 degrees C, indicating that these trout swim more efficiently than those from the Little Blitzen. Possible explanations for the greater metabolic power of Little Blitzen redband trout at 12 degrees C include increased relative ventricular mass (27%) and an elevation in epaxial white muscle citrate synthase activity (by 72%). Bridge Creek trout had 50% higher lactate dehydrogenase activity in white muscle and presumably a greater potential for anaerobic metabolism. Both populations exhibited a preferred temperature of approximately 13 degrees C and identical mitochondrial haplotypes and p53 gene allele frequencies. However, Bridge Creek trout had a more robust body form, with a relatively larger head and a deeper body and caudal peduncle. In summary, despite the short distance ( approximately 10 km) and genotypic similarity between study streams, our results indicate that phenotypic reorganization of anatomical characteristics, swimming ability at environmentally pertinent temperatures and white axial muscle ATP-producing pathways occurs in redband trout.

Purpose: To compare T2-weighted breath-hold single-shot fast spin-echo (SE) and gadolinium-enhanced spoiled gradient-echo (GRE) MR imaging with contrast material administered orally and rectally for evaluating patients with Crohn disease., Materials and Methods: Twenty-eight patients with Crohn disease received 2% barium sulfate and water enema. The abdomen and pelvis were imaged with transverse and coronal single-shot fast SE and gadolinium-enhanced spoiled GRE MR imaging. Two radiologists reviewed the two types of images for bowel disease. The extent, severity, and conspicuity of the disease were determined. Proof of bowel disease at MR imaging was compared with that at endoscopy, barium study, and surgery. Statistical analysis was performed with the McNemar test., Results: Twenty-five of 28 patients had proven abnormal bowel segments. The per-patient sensitivity of gadolinium-enhanced spoiled GRE MR imaging for the two radiologists was 100% and 96% versus 60% and 60% (P <.05) with single-shot fast SE MR imaging. Gadolinium-enhanced spoiled GRE MR images depicted more segments (54 and 52 of 61 segments; sensitivity, 89% and 85%, respectively) of the diseased bowel than did single-shot fast SE MR images (31 and 32 of 61 segments; sensitivity, 51% and 52%, respectively; P <.001). Severity of Crohn disease was correctly depicted at gadolinium-enhanced spoiled GRE imaging in 93% of patients versus in 43% of patients at single-shot fast SE imaging., Conclusion: In patients with Crohn disease, gadolinium-enhanced fat-suppressed spoiled GRE MR imaging better depicted the extent and severity of intestinal disease compared with single-shot fast SE imaging.

Sixty patients were evaluated for acute abdominal pain using technetium-99m PIPIDA hepatobiliary imaging. The sensitivity of the test was 90.6 percent in all patients and the accuracy was 93.3 percent. In the evaluation of acutely ill patients with right upper quadrant pain, fever, nausea and vomiting, hepatobiliary imaging with PIPIDA is the preferred test for diagnosing acute cholecystitis. If the test is positive, disease of the gallbladder and probably acute cholecystitis are present. Early operation can proceed if desirable. If the test is negative and the bilirubin level is less than 5.0 mg/dl, acute cholecystitis is not present. In such cases conservative treatment is appropriate, and follow-up tests should be performed to evaluate the possibility of chronic cholecystitis. When the bilirubin level exceeds 5.0 mg/dl, the test is often indeterminate.