Assessing the Risks Associated with MRI in Patients with a Pacemaker or Defibrillator.

BACKGROUND: The presence of a cardiovascular implantable electronic device has long been a contraindication for the performance of magnetic resonance imaging (MRI). We established a prospective registry to determine the risks associated with MRI at a magnetic field strength of 1.5 tesla for patients who had a pacemaker or implantable cardioverter-defibrillator (ICD) that was "non-MRI-conditional" (i.e., not approved by the Food and Drug Administration for MRI scanning). METHODS: Patients in the registry were referred for clinically indicated nonthoracic MRI at a field strength of 1.5 tesla. Devices were interrogated before and after MRI with the use of a standardized protocol and were appropriately reprogrammed before the scanning. The primary end points were death, generator or lead failure, induced arrhythmia, loss of capture, or electrical reset during the scanning. The secondary end points were changes in device settings. RESULTS: MRI was performed in 1000 cases in which patients had a pacemaker and in 500 cases in which patients had an ICD. No deaths, lead failures, losses of capture, or ventricular arrhythmias occurred during MRI. One ICD generator could not be interrogated after MRI and required immediate replacement; the device had not been appropriately programmed per protocol before the MRI. We observed six cases of self-terminating atrial fibrillation or flutter and six cases of partial electrical reset. Changes in lead impedance, pacing threshold, battery voltage, and P-wave and R-wave amplitude exceeded prespecified thresholds in a small number of cases. Repeat MRI was not associated with an increase in adverse events. CONCLUSIONS: In this study, device or lead failure did not occur in any patient with a non-MRI-conditional pacemaker or ICD who underwent clinically indicated nonthoracic MRI at 1.5 tesla, was appropriately screened, and had the device reprogrammed in accordance with the prespecified protocol. (Funded by St. Jude Medical and others; MagnaSafe ClinicalTrials.gov number, NCT00907361 .).

Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

OBJECTIVE: To review the literature systematically to determine whether noninvasive or invasive risk stratification, such as with an electrophysiological study of patients with asymptomatic pre-excitation, reduces the risk of arrhythmic events and improves patient outcomes. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (all January 1, 1970, through August 31, 2014) were searched for randomized controlled trials and cohort studies examining noninvasive or invasive risk stratification in patients with asymptomatic pre-excitation. Studies were rejected for low-quality design or the lack of an outcome, population, intervention, or comparator of interest or if they were written in a language other than English. RESULTS: Of 778 citations found, 9 studies met all the eligibility criteria and were included in this paper. Of the 9 studies, 1 had a dual design-a randomized controlled trial of ablation versus no ablation in 76 patients and an uncontrolled prospective cohort of 148 additional patients-and 8 were uncontrolled prospective cohort studies (n=1594). In studies reporting a mean age, the range was 32 to 50 years, and in studies reporting a median age, the range was 19 to 36 years. The majority of patients were male (range, 50% to 74%), and <10% had structural heart disease. In the randomized controlled trial component of the dual-design study, the 5-year Kaplan-Meier estimates of the incidence of arrhythmic events were 7% among patients who underwent ablation and 77% among patients who did not undergo ablation (relative risk reduction: 0.08; 95% confidence interval: 0.02 to 0.33; P<0.001). In the observational cohorts of asymptomatic patients who did not undergo catheter ablation (n=883, with follow-up ranging from 8 to 96 months), regular supraventricular tachycardia or benign atrial fibrillation (shortest RR interval >250 ms) developed in 0% to 16%, malignant atrial fibrillation (shortest RR interval ≤250 ms) in 0% to 9%, and ventricular fibrillation in 0% to 2%, most of whom were children in the last case. CONCLUSIONS: The existing evidence suggests risk stratification with an electrophysiological study of patients with asymptomatic pre-excitation may be beneficial, along with consideration of accessory-pathway ablation in those deemed to be at high risk of future arrhythmias. Given the limitations of the existing data, well-designed and well-conducted studies are needed.

Sex Differences in Device Therapies for Ventricular Arrhythmias or Death in the Multicenter Automatic Defibrillator Implantation Trial With Cardiac Resynchronization Therapy (MADIT-CRT) Trial.

INTRODUCTION: Studies suggest that women with ischemic heart disease are less likely to experience appropriate ICD therapies for ventricular arrhythmias (VT/VF). We evaluated the influence of sex on arrhythmic events or death in subjects enrolled in MADIT-CRT. METHODS AND RESULTS: Arrhythmic event rates, defined as VT/VF treated with defibrillator therapy or all-cause death, were determined among 1,790 subjects enrolled in MADIT-CRT with documented 3-year follow-up. Predictors of VT/VF/death were identified using multivariate analysis. Ninety-one (21%) women and 466 (35%) men experienced VT/VF/death over the follow-up period. The overall probability of VT/VF/death was significantly lower in women versus men (HR 0.62; P < 0.001). The probability of VT/VF/death was the lowest in women with ischemic heart disease (HR 0.51; P = 0.003). In ICD subjects, the 3-year risk of VT/VF was lower in ischemic women versus men (P = 0.021), and in nonischemic women versus men (P = 0.049). The probability of VT/VF/death was significantly lower in women (HR 0.52; P = 0.007) and men (HR 0.74; P = 0.018) with LBBB who received CRT-D. Appropriate shock therapy strongly correlated with increased risk of death during postshock follow-up in women (HR 5.18; P = 0.001) and men (HR 1.63; P = 0.033); interaction P value of 0.034. CONCLUSION: In this substudy of MADIT-CRT, sex, etiology of heart disease and type of device implanted significantly influenced subsequent risk for VT/VF or death. Women with ischemic heart disease and women with LBBB who received CRT-D had the lowest incidence of VT/VF or death when compared to men. Appropriate shock therapy was a strong predictor of death, particularly in women.

Comparative safety of periablation anticoagulation strategies for atrial fibrillation: data from a large multicenter study.

BACKGROUND: There are a variety of periprocedural anticoagulation strategies for atrial fibrillation (AF) ablation, including the use of dabigatran. It is unclear which strategy is superior. OBJECTIVE: To compare the safety and efficacy of anticoagulation with uninterrupted warfarin, dabigatran, and warfarin with heparin bridging in patients undergoing ablation of AF at four experienced centers. METHODS AND RESULTS: In this retrospective analysis, 882 patients (mean age: 61 ± 11 years) underwent ablation of AF using uninterrupted warfarin (n = 276), dabigatran (n = 374), or warfarin with heparin bridging (n = 232) for periprocedural anticoagulation. The rate of total complications was 23/276 (8.3%) in the uninterrupted warfarin group, 30/374 (8.0%) in the dabigatran group, and 29/232 (12.5%) in the bridged group (P = 0.15). Major complications were more frequent in the uninterrupted warfarin group 12/276 (4.3%) compared with 3/374 (0.8%) in dabigatran and 6/232 (2.6%) in the bridged group (P = 0.01). The most common major complication was the need for transfusion or occurrence of major bleeding. Minor complications did not differ among the three groups. On multivariate analysis, female gender (odds ratio [OR] 1.93, confidence interval [CI] 1.16-3.19, P = 0.011), bridging heparin (OR 2.13, CI 1.100-3.941, P = 0.016), use of triple antithrombotic therapy (OR 1.77, CI 1.05-2.98, P = 0.033), and prior myocardial infarction (OR 2.40, CI 1.01-5.67, P = 0.046) independently predicted total complications. CONCLUSIONS: When comparing the use of uninterrupted warfarin, dabigatran, and warfarin with heparin bridging in patients undergoing catheter ablation of AF, dabigatran was not associated with increased risk, major complications were more common in the uninterrupted warfarin group, and after adjustment, warfarin with bridging increased total complications.

Challenge Accepted: Lead Extraction in a Patient with Persistent Left Superior Vena Cava and Right Superior Vena Cava Occlusion.

Persistent left superior vena cava (PLSVC) is an anatomic variant that is relatively uncommon in the general population. Lead extraction through PLSVC is extremely rare. Due to unusual anatomy, the procedure carries challenges that require special considerations and careful planning. The authors report a case of lead extraction through a PLSVC with occluded right superior vena cava and highlight the challenges and outcomes of the procedure.

Dissecting antibiotic effects on the cell envelope using bacterial cytological profiling: a phenotypic analysis starter kit.

Phenotypic analysis assays such as bacterial cytological profiling (BCP) have become increasingly popular for antibiotic mode of action analysis. A plethora of dyes, protein fusions, and reporter strains are available and have been used for this purpose, enabling both rapid mode of action categorization and in-depth analysis of antibiotic mechanisms. However, non-expert researchers may struggle choosing suitable assays and interpreting results. This is a particular problem for antibiotics that have multiple or complex targets, such as the bacterial cell envelope. Here, we set out to curate a minimal set of accessible and affordable phenotypic assays that allow distinction between membrane and cell wall targets, can identify dual-action inhibitors, and can be implemented in most research environments. To this end, we employed BCP, membrane potential, fluidity, and cell wall synthesis assays. To assess specificity and ease of interpretation, we tested three well-characterized and commercially available reference antibiotics: the potassium ionophore valinomycin, the lipid II-binding glycopeptide vancomycin, and the dual-action lantibiotic nisin, which binds lipid II and forms a membrane pore. Based on our experiments, we suggest a minimal set of BCP, a membrane-potentiometric probe, and fluorescent protein fusions to MinD and MreB as basic assay set and recommend complementing these assays with Laurdan-based fluidity measurements and a PliaI reporter fusion, where indicated. We believe that our results can provide guidance for researchers who wish to use phenotypic analysis for mode of action studies but do not possess the specialized equipment or expert knowledge to employ the full breadth of possible techniques.IMPORTANCEPhenotypic analysis assays using specialized fluorescence fusions and dyes have become increasingly popular in antibiotic mode of action analysis. However, it can be difficult to implement these methods due to the need for specialized equipment and/or the complexity of bacterial cell biology and physiology, making the interpretation of results difficult for non-experts. This is especially problematic for compounds that have multiple or pleiotropic effects, such as inhibitors of the bacterial cell envelope. In order to make phenotypic analysis assays accessible to labs, whose primary expertise is not bacterial cell biology, or with limited equipment and resources, a set of simple and broadly accessible assays is needed that is easy to implement, execute, and interpret. Here, we have curated a set of assays and strains that does not need highly specialized equipment, can be performed in most labs, and is straightforward to interpret without knowing the intricacies of bacterial cell biology.

Resumption of sinus rhythm in patients with heart failure and permanent atrial fibrillation undergoing cardiac resynchronization therapy: a longitudinal observational study.

AIMS: To investigate the temporal patterns, predictors, and prognostic impact of spontaneous sinus rhythm resumption (SRR) of heart failure (HF) patients with permanent atrial fibrillation (AF) treated with cardiac resynchronization therapy (CRT). METHODS AND RESULTS: This multicentre, retrospective, longitudinal study analysed 330 consecutive HF patients with permanent AF treated with a CRT device (mean age 70 +/- 9 years, male 83%, ischaemic aetiology 44%, NYHA class III-IV 93%, mean QRS duration 167 +/- 40 ms, and mean ejection fraction 26 +/- 7%). Clinical, echocardiographic, and outcome data were collected during follow-up. Thirty-four patients experienced SRR after CRT (10.3%) at a median 4-month follow-up. The strongest independent predictors were end-diastolic diameter (EDD) [hazard ratios (HR) 4.03, 95% confidence intervals (95% CI) 1.43-11.36, P = 0.008], post-CRT QRS

Alleviation of C⋠C Mismatches in DNA by the Escherichia coli Fpg Protein.

DNA polymerase III mis-insertion may, where not corrected by its 3'→ 5' exonuclease or the mismatch repair (MMR) function, result in all possible non-cognate base pairs in DNA generating base substitutions. The most thermodynamically unstable base pair, the cytosine (C)⋅C mismatch, destabilizes adjacent base pairs, is resistant to correction by MMR in Escherichia coli, and its repair mechanism remains elusive. We present here in vitro evidence that C⋅C mismatch can be processed by base excision repair initiated by the E. coli formamidopyrimidine-DNA glycosylase (Fpg) protein. The k cat for C⋅C is, however, 2.5 to 10 times lower than for its primary substrate 8-oxoguanine (oxo8G)⋅C, but approaches those for 5,6-dihydrothymine (dHT)⋅C and thymine glycol (Tg)⋅C. The K M values are all in the same range, which indicates efficient recognition of C⋅C mismatches in DNA. Fpg activity was also exhibited for the thymine (T)⋅T mismatch and for N 4- and/or 5-methylated C opposite C or T, Fpg activity being enabled on a broad spectrum of DNA lesions and mismatches by the flexibility of the active site loop. We hypothesize that Fpg plays a role in resolving C⋅C in particular, but also other pyrimidine⋅pyrimidine mismatches, which increases survival at the cost of some mutagenesis.

Computational method to predict esophageal temperature elevations during pulmonary vein isolation.

BACKGROUND: The esophagus is in close proximity to the posterior wall of the left atrium, which renders it susceptible to thermal injury during radiofrequency (RF) ablation procedures for atrial fibrillation (AF). Real-time assessment of esophageal position and temperature (T°) during pulmonary vein (PV) isolation has not been extensively explored. OBJECTIVE: To develop a protocol that allows estimation of the potential for, and avoidance of, esophageal heating. METHODS: In consecutive patients who underwent PV isolation, a thermal probe was used to monitor T° fluctuations in the esophagus during application of RF energy. The tip of the thermal probe was positioned at the level of the targeted PV and RF was discontinued for T° rise >0.5°C. The proximity of individual PVs to the esophagus was measured from the temperature probe tip to the closest posterior part of the Lasso catheter from review of biplane projections (left anterior oblique 60° and right anterior oblique 30°). These raw distances were entered into the Pythagorean theorem and the actual distance between the esophageal thermal probe and PV antrum was determined. RESULTS: The study cohort included 44 patients (60 ± 11 years, 61% male, 57% lone AF). The thermal probe in the esophagus was closer to the left-sided PVs (left common pulmonary vein: 20.9 ± 13 mm, left upper pulmonary vein: 20.5 ± 11 mm, left lower pulmonary vein: 23.4 ± 10 mm) than the right-sided ones (right common pulmonary vein: 31.0 ± 11 mm, right upper pulmonary vein: 41.9 ± 18 mm, right lower pulmonary vein: 34.5 ± 16 mm). A T° increase >0.5° C occurred during 116/1,495 (7.8%) deliveries. A T° rise was more likely during ablation of left-sided PVs than right-sided PVs (55% vs 10%, P < 0.0001) and when RF was delivered ≤ 24 mm from the esophagus (sensitivity 91%, specificity 81%, positive predictive value 75%, and negative predictive value 93%). CONCLUSION: A thermal probe placed in the esophagus provides real-time T° monitoring and anatomic localization. A T° rise is more likely during ablation of left PVs and during RF deliveries within 24 mm of the esophageal thermal probe.

Analysis of Tuberculosis Meningitis Pathogenesis, Diagnosis, and Treatment.

Tuberculosis (TB) is the most prevalent infectious disease in the world. In recent years there has been a significant increase in the incidence of TB due to the emergence of multidrug resistant strains of Mycobacterium tuberculosis (M. tuberculosis) and the increased numbers of highly susceptible immuno-compromised individuals. Central nervous system TB, includes TB meningitis (TBM-the most common presentation), intracranial tuberculomas, and spinal tuberculous arachnoiditis. Individuals with TBM have an initial phase of malaise, headache, fever, or personality change, followed by protracted headache, stroke, meningismus, vomiting, confusion, and focal neurologic findings in two to three weeks. If untreated, mental status deteriorates into stupor or coma. Delay in the treatment of TBM results in, either death or substantial neurological morbidity. This review provides latest developments in the biomedical research on TB meningitis mainly in the areas of host immune responses, pathogenesis, diagnosis, and treatment of this disease.

Long-term outcome following successful pulmonary vein isolation: pattern and prediction of very late recurrence.

BACKGROUND: Despite encouraging results of pulmonary vein isolation (PVI) ablation for atrial fibrillation (AF), it is unclear whether there is genuine cure or there is an important attrition rate. We sought to determine the long-term outcome of the initial responders who experienced a prolonged AF-free complete response. METHODS: From a series of 350 consecutive patients who underwent PVI for AF, 264 patients (75%) (males 71%, age 57 +/- 12 years, paroxysmal AF 87%) who demonstrated >or=1 year AF-free follow-up on no antiarrhythmic drugs were followed for 1-5 years. RESULTS: During 28 +/- 12 months follow-up, 23 of 264 (8.7%) patients had recurrence of AF. The actuarial recurrence at 2 years postablation was 5.8% and increased to 25.5% at 5 years. Compared with long-term responders, more patients with late recurrence had hypertension (HR = 2.18, P = 0.009) and hyperlipidemia (HR = 4.01, P = 0.0005). Among 18 patients with recurrent AF necessitating repeat PVI, 15 (83%) required re-isolation of > 1 PV and 28 of 45 (58%) PVs showed reconnection. All PVs were re-isolated and five (28%) patients had additional linear ablation. All 15 patients became AF-free again. CONCLUSIONS: Although most patients following PVI remain AF-free, some patients develop "late" recurrence of AF. The "late" recurrence patients are more likely to have hypertension and hyperlipidemia. Most late recurrences are associated with PV reconnections. Our observations emphasize the importance of continued long-term vigilance for AF recurrence, and also raise concerns regarding the need for long-term anticoagulation therapy.

An innovative approach to identifying learning needs for intrinsic CanMEDS roles in continuing professional development.

CONTEXT: The CanMEDS framework promotes the development of competencies required to be an effective physician. However, it is still not well understood how to apply such frameworks to CPD contexts, particularly with respect to intrinsic competencies. OBJECTIVE: This study explores whether physician narratives around challenging cases would provide information regarding learning needs that could help guide the development of CPD activities for intrinsic CanMEDS competencies. METHODS: We surveyed medical and surgical specialists from Southern Ontario using an online survey. To assess perceived needs, participants were asked, 'Describe three CPD topic you would like to learn about in the next 12 months'. To identify learning needs that may have arisen from problems encountered in practice, participants were asked, 'Describe three challenging situations encountered in the past 12 months.' Responses to the two open-ended questions were analyzed using thematic content analysis. RESULTS: Responses were received from 411 physicians, resulting in 226 intrinsic CanMEDS codes for perceived learning needs and 210 intrinsic codes for challenges encountered in practices. Discrepancies in the frequency of intrinsic roles were observed between the two questions. Specifically, Leader (28%), Scholar (43%), and Professional (16%) roles were frequently described perceived learning needs, as opposed to challenges in practice (Leader: 3%; Scholar: 2%; and Professional: 8%. Conversely, Communicator 39%, Health Advocate 39%, and to a lesser extent Collaborator 11%) roles were frequently described in narratives surrounding challenges in practice, but appeared in <10% of descriptions of perceived learning needs (Communicator: 4%; Health Advocate 6%; Collaborator: 3%). CONCLUSION: The present study provides insight into potential learning needs associated with intrinsic CanMEDS competencies. Discrepancies in the frequency of intrinsic CanMEDS roles coded for perceived learning needs and challenges encountered in practice may provide insight into the selection and design of CPD activities.

Excision of the doubly methylated base N4,5-dimethylcytosine from DNA by Escherichia coli Nei and Fpg proteins.

Cytosine (C) in DNA is often modified to 5-methylcytosine (m5C) to execute important cellular functions. Despite the significance of m5C for epigenetic regulation in mammals, damage to m5C has received little attention. For instance, almost no studies exist on erroneous methylation of m5C by alkylating agents to doubly or triply methylated bases. Owing to chemical evidence, and because many prokaryotes express methyltransferases able to convert m5C into N4,5-dimethylcytosine (m N4,5C) in DNA, m N4,5C is probably present in vivo We screened a series of glycosylases from prokaryotic to human and found significant DNA incision activity of the Escherichia coli Nei and Fpg proteins at m N4,5C residues in vitro The activity of Nei was highest opposite cognate guanine followed by adenine, thymine (T) and C. Fpg-complemented Nei by exhibiting the highest activity opposite C followed by lower activity opposite T. To our knowledge, this is the first description of a repair enzyme activity at a further methylated m5C in DNA, as well as the first alkylated base allocated as a Nei or Fpg substrate. Based on our observed high sensitivity to nuclease S1 digestion, we suggest that m N4,5C occurs as a disturbing lesion in DNA and that Nei may serve as a major DNA glycosylase in E. coli to initiate its repair.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'.

Focal impulse and rotor modulation: Acute procedural observations and extended clinical follow-up.

BACKGROUND: Focal impulse and rotor modulation (FIRM) was based on the premise that atrial fibrillation (AF) is sustained by rotors that are sufficiently stable to be eliminated by targeted ablation. Early experience reported high success as compared to conventional strategies. OBJECTIVE: The purpose of this study was to report on a single-center experience with extended follow-up by using FIRM in a variety of patients with AF. METHODS: All FIRM-guided ablation procedures were included. During spontaneous or induced AF, FIRM software constructed phase maps to identify putative AF sources, then targeted for radiofrequency ablation, with adjunctive pulmonary vein isolation (PVI), if needed. All mapped rotors and/or sources were eliminated on the basis of repeated FIRM mapping. RESULTS: Of 47 patients, sustained AF was not present or induced in 4 patients who did not undergo FIRM ablation. Of the remaining 43 patients, prior AF was paroxysmal in 9 (21%) and 72% had a median of 1 prior PVI. Spontaneous AF (n = 22, 52%) and induced AF (n = 21, 49%) were mapped, and all patients had rotors identified (1.8 ± 0.8 per patient; 70% in the left atrium). AF termination occurred in 2 patients (5%) and none organized to atrial tachycardia. Touch-up redo PVI was also performed in 31 patients (72%). At 16.0 ± 10.7 months (range 1-34 months), only 9 patients (21%) were free of recurrent AF; and only 5 patients (12%) were free of AF and off antiarrhythmic drugs. CONCLUSION: Long-term clinical results after FIRM ablation in this diverse challenging cohort showed poor efficacy. Randomized clinical trials are needed to evaluate the efficacy and clinical utility of the FIRM ablation approach for treating AF.

Risk stratification for arrhythmic events in patients with asymptomatic pre-excitation: A systematic review for the 2015 ACC/AHA/HRS guideline for the management of adult patients with supraventricular tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

OBJECTIVE: To review the literature systematically to determine whether noninvasive or invasive risk stratification, such as with an electrophysiological study of patients with asymptomatic pre-excitation, reduces the risk of arrhythmic events and improves patient outcomes. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (all January 1, 1970, through August 31, 2014) were searched for randomized controlled trials and cohort studies examining noninvasive or invasive risk stratification in patients with asymptomatic pre-excitation. Studies were rejected for low-quality design or the lack of an outcome, population, intervention, or comparator of interest or if they were written in a language other than English. RESULTS: Of 778 citations found, 9 studies met all the eligibility criteria and were included in this paper. Of the 9 studies, 1 had a dual design-a randomized controlled trial of ablation versus no ablation in 76 patients and an uncontrolled prospective cohort of 148 additional patients-and 8 were uncontrolled prospective cohort studies (n=1,594). In studies reporting a mean age, the range was 32 to 50 years, and in studies reporting a median age, the range was 19 to 36 years. The majority of patients were male (range, 50% to 74%), and <10% had structural heart disease. In the randomized controlled trial component of the dual-design study, the 5-year Kaplan-Meier estimates of the incidence of arrhythmic events were 7% among patients who underwent ablation and 77% among patients who did not undergo ablation (relative risk reduction: 0.08; 95% confidence interval: 0.02 to 0.33; p<0.001). In the observational cohorts of asymptomatic patients who did not undergo catheter ablation (n=883, with follow-up ranging from 8 to 96 months), regular supraventricular tachycardia or benign atrial fibrillation (shortest RR interval >250 ms) developed in 0% to 16%, malignant atrial fibrillation (shortest RR interval ≤250 ms) in 0% to 9%, and ventricular fibrillation in 0% to 2%, most of whom were children in the last case. CONCLUSIONS: The existing evidence suggests risk stratification with an electrophysiological study of patients with asymptomatic pre-excitation may be beneficial, along with consideration of accessory-pathway ablation in those deemed to be at high risk of future arrhythmias. Given the limitations of the existing data, well-designed and well-conducted studies are needed.

Risk Stratification for Arrhythmic Events in Patients With Asymptomatic Pre-Excitation: A Systematic Review for the 2015 ACC/AHA/HRS Guideline for the Management of Adult Patients With Supraventricular Tachycardia: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society.

OBJECTIVE: To review the literature systematically to determine whether noninvasive or invasive risk stratification, such as with an electrophysiological study of patients with asymptomatic pre-excitation, reduces the risk of arrhythmic events and improves patient outcomes. METHODS: PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials (all January 1, 1970, through August 31, 2014) were searched for randomized controlled trials and cohort studies examining noninvasive or invasive risk stratification in patients with asymptomatic pre-excitation. Studies were rejected for low-quality design or the lack of an outcome, population, intervention, or comparator of interest or if they were written in a language other than English. RESULTS: Of 778 citations found, 9 studies met all the eligibility criteria and were included in this paper. Of the 9 studies, 1 had a dual design-a randomized controlled trial of ablation versus no ablation in 76 patients and an uncontrolled prospective cohort of 148 additional patients-and 8 were uncontrolled prospective cohort studies (n=1,594). In studies reporting a mean age, the range was 32 to 50 years, and in studies reporting a median age, the range was 19 to 36 years. The majority of patients were male (range, 50% to 74%), and <10% had structural heart disease. In the randomized controlled trial component of the dual-design study, the 5-year Kaplan-Meier estimates of the incidence of arrhythmic events were 7% among patients who underwent ablation and 77% among patients who did not undergo ablation (relative risk reduction: 0.08; 95% confidence interval: 0.02 to 0.33; p<0.001). In the observational cohorts of asymptomatic patients who did not undergo catheter ablation (n=883, with follow-up ranging from 8 to 96 months), regular supraventricular tachycardia or benign atrial fibrillation (shortest RR interval >250 ms) developed in 0% to 16%, malignant atrial fibrillation (shortest RR interval ≤250 ms) in 0% to 9%, and ventricular fibrillation in 0% to 2%, most of whom were children in the last case. CONCLUSIONS: The existing evidence suggests risk stratification with an electrophysiological study of patients with asymptomatic pre-excitation may be beneficial, along with consideration of accessory-pathway ablation in those deemed to be at high risk of future arrhythmias. Given the limitations of the existing data, well-designed and well-conducted studies are needed.

The World Trade Center attack: increased frequency of defibrillator shocks for ventricular arrhythmias in patients living remotely from New York City.

OBJECTIVES: The goal of this study was to determine whether the World Trade Center (WTC) attack on September 11, 2001, had an effect on the occurrence of ventricular arrhythmias among patients with implantable cardioverter-defibrillators (ICDs) living in Florida. BACKGROUND: Increased frequencies of ICD therapies for ventricular arrhythmias were reported among patients in New York City after the attack on the WTC. Whether this effect also occurred in patients living geographically distant from New York is unknown. METHODS: This was an observational study consisting of 132 ICD patients who presented to the University of Florida and the Veterans Affairs Medical Center in Gainesville, Florida, for routine ICD follow-up around the time of the WTC attack. The occurrence of ventricular tachyarrhythmias triggering ICD therapy in the 30 days before and after September 11 constituted the primary end point. RESULTS: In the 30 days following the WTC attack, a total of 14 patients (11%) had ventricular tachyarrhythmias, compared with 5 (3.8%) in the preceding 30 days (p = 0.0389, 95% confidence interval [CI] 0.4 to 13.3). This represents a 2.8-fold risk increase. Patients with ventricular arrhythmias both before and after September 11 demonstrated a rate increase of 2.38 events per patient (p = 0.0231, 95% CI 1.03 to 13.97). CONCLUSIONS: The frequency of ventricular arrhythmias requiring ICD treatment increased by 68% among patients in Florida around the WTC attack. These findings suggest that stress-related arrhythmogenesis due to the WTC tragedy was not restricted to the geographic location of the attack. A major national tragedy may cause widespread increased risk of potentially life-threatening ventricular arrhythmias.

Increased incidence of life-threatening ventricular arrhythmias in implantable defibrillator patients after the World Trade Center attack.

OBJECTIVES: This study was designed to evaluate whether the destruction of the World Trade Center (WTC) on September 11, 2001 (9/11), led to an increased frequency of ventricular arrhythmias among patients fitted with an implantable cardioverter-defibrillator (ICD). BACKGROUND: The WTC attack induced psychological distress. Because ICDs store all serious arrhythmias for months, the attack provided a unique opportunity to compare pre- and post-9/11 frequencies of potentially lethal arrhythmias among ICD patients. METHODS: Two hundred consecutive ICD patients who presented for regularly scheduled follow-up to six affiliated clinics were recruited into this observational study. The electrograms stored in the ICDs for the three months before 9/11 and 13 months thereafter were scrutinized in a blinded manner (relative to date) for all ventricular tachyarrhythmias (tachycardia or fibrillation) triggering ICD therapy. RESULTS: The frequency of tachyarrhythmias increased significantly for the 30 days post-9/11 (p = 0.004) relative to all other months between May 2001 and October 2002. In the 30 days post-9/11, 16 patients (8%) demonstrated tachyarrhythmias, compared with only seven (3.5%) in the preceding 30 days, representing a 2.3-fold increase in risk (95% confidence interval 1.1 to 4.9; p = 0.03). The first arrhythmic event did not occur for three days following 9/11, with events accumulating in a progressive non-clustered pattern. CONCLUSIONS: Ventricular arrhythmias increased by more than twofold among ICD patients following the WTC attack. The delay in onset and the non-clustered pattern of these events differ sharply from effects following other disasters, suggesting that subacute stress may have served to promote this arrhythmogenesis.