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While obesity has been shown to be associated with elevated risk for Sudden Cardiac Death (SCD), studies examining its effect on outcomes in SCD victims have shown conflicting results. We aimed to describe the body mass index (BMI) distribution in a nationwide cohort of patients admitted for an out of hospital SCD (OHSCD), and the relationship between BMI and in‐hospital mortality. We drew data from the U.S. National Inpatient Sample (NIS), to identify cases of OHSCD. Patients were divided into six groups based on their BMI (underweight, normal weight, overweight, obese I, obese II, extremely obese). Socio‐demographic and clinical data were collected, mortality and length of stay were analyzed. Multivariate analysis was performed to identify predictors of mortality. Among a weighted total of 2330 hospitalizations for OHSCD in patients with documented BMI, the mean age was 62.3 ± 29 years, 52.4% were male and 62% were white. The overall rate of in‐hospital mortality was 69.3%. A U‐shaped relationship between the BMI and mortality was documented, as patients with 25

BACKGROUND Catheter ablation (CA) for ventricular arrhythmias (VAs) is increasingly utilized in recent years. We aimed to investigate the nationwide trends in utilization and procedural complications of CA for VAs in patients with mechanical valve (MV) prosthesis. METHODS We drew data from the US National Inpatient Sample database to identify cases of VA ablations, including premature ventricular contraction and ventricular tachycardia, in patients with MVs, between 2003 and 2015. Sociodemographic and clinical data were collected and the incidence of catheter ablation complications, mortality, and length of stay were analyzed. We compared the outcomes to a propensity-matched cohort of patients without prior valve surgery. RESULTS The study population included a weighted total of 647 CA cases in patients with prior MVs. The annual number of ablations almost doubled, from 34 ablations on average during the "early years" (2003-2008) to 64 on average during the "late years" (2009-2015) of the study (p = .001). Length of stay at the hospital did not differ significantly between patients with MVs and 649 matched patients without prior MVs (5.4 ± 0.4, 4.7 ± 0.3 days, respectively, p = .12). The data revealed a trend toward a higher incidence of complications (12.6% vs. 7.5% respectively, p = .14) and mortality (3.7% vs. 0.7%, respectively, p = .087) among patients with MVs compared to the matched control group, not reaching statistical significance. CONCLUSION The data show increased utilization of VA ablations in patients with MVs and a trend toward a higher incidence of in-hospital mortality and complications compared to the propensity-matched control group without MVs.

Left atrial appendage closure (LAAC) is an important strategy to reduce stroke risk in patients with non-valvular atrial fibrillation (AF) who are at high risk of bleeding on long-term anticoagulation. Real-world assessments of the safety of the Watchman LAAC device remain limited. The objective of this study was to determine the frequency and timing of adverse events associated with Watchman LAAC device implants performed after FDA approval. Adverse events associated with Watchman LAAC implants performed between March 2015 and March 2019 were identified through a search of the FDA Manufacturer and User Facility Device Experience (MAUDE) database. During the study period, 3,652 unique adverse events were identified. An estimated 43,802 Watchman implants were performed in the United States during the study period. The overall adverse event rate was 7.3% and the mortality rate was 0.4%. Of the 159 unique types of adverse events identified, pericardial effusion was most common (1.4%). Most adverse events (73%) occurred intraoperatively (59%) or within 1 day of the procedure (15%). However, 19% of deaths, 24% of strokes and 27% of device embolizations occurred >1 month after implantation. The rates of most Watchman-related adverse events reported in the MAUDE database were comparable to those observed in clinical trials. A majority of adverse events occurred within 1 day of implant. In conclusion, while the absolute event rates were low, a significant proportion of device embolizations, strokes, and deaths occurred >1 month after Watchman implant.

We report a case of catheter ablation of Brugada syndrome in a patient with refractory ventricular fibrillation despite quinidine therapy. We performed epicardial substrate mapping, which identified an area of abnormal fractionated, prolonged electrogram in the anterior right ventricular outflow tract. Warm saline infusion into the pericardial space induced further delay of the local electrogram, consistent with Brugada syndrome physiology. Coronary angiography confirmed that the area was distant from major coronary arteries. Ablation was performed in this area, which eliminated local abnormal electrograms and led to the disappearance of coved-type ST elevation in V1–V2. No ventricular fibrillation had recurred by five months of follow-up.

Eliglustat is a first-line oral treatment for adults with Gaucher disease type 1 who have cytochrome P450 (CYP) 2D6 extensive, intermediate, or poor metabolizer phenotypes. Per International Conference on Harmonisation (ICH) E14 guidance, a Phase 1 thorough electrocardiographic (ECG) study was done during drug development to assess eliglustat's effects on cardiac repolarization by measuring ECG intervals in healthy adult subjects. Using data from the thorough ECG study, we performed pharmacokinetic/pharmacodynamic-ECG modeling to establish the relationship between eliglustat concentrations and their effects on ECG intervals. We then used that concentration-response relationship to predict the effects of eliglustat on each ECG interval for each CYP2D6 metabolizer phenotype (the main determinant of eliglustat exposure) and in different drug-drug interaction scenarios. These predictions, together with other exposure-related factors, contributed to the CYP2D6 phenotype-based dosing recommendations for eliglustat, including dose adjustments and contraindications when co-administered with drugs metabolized by the CYP2D6 and CYP3A pathways.

Background Lyme carditis, defined as direct infection of cardiac tissue by Borrelia bacteria, affects up to 10% of patients with Lyme disease. The most frequently reported clinical manifestation of Lyme carditis is cardiac conduction system disease. The goal of this study was to identify the incidence and predictors of permanent pacemaker implantation in patients hospitalized with Lyme disease. Methods A retrospective cohort analysis of the Nationwide Inpatient sample was performed to identify patients hospitalized with Lyme disease in the US between 2003 and 2014. Patients with Lyme carditis were defined as those hospitalized with Lyme disease who also had cardiac conduction disease, acute myocarditis, or acute pericarditis. Patients who already had pacemaker implants at the time of hospitalization (N = 310) were excluded from the Lyme carditis subgroup. The primary study outcome was permanent pacemaker implantation. Secondary outcomes included temporary cardiac pacing, permanent pacemaker implant, and in-hospital mortality. Results Of the 96,140 patients hospitalized with Lyme disease during the study period, 10,465 (11%) presented with Lyme carditis. Cardiac conduction system disease was present in 9,729 (93%) of patients with Lyme carditis. Permanent pacemaker implantation was performed in 1,033 patients (1% of all Lyme hospitalizations and 11% of patients with Lyme carditis-associated conduction system disease). Predictors of permanent pacemaker implantation included older age (OR: 1.06 per 1 year; 95% CI:1.05–1.07; P Conclusions Approximately 11% of patients hospitalized with Lyme disease present with carditis, primarily in the form of cardiac conduction system disease. In this 12-year study, 1% of all hospitalized patients and 11% of those with Lyme-associated cardiac conduction system disease underwent permanent pacemaker implantation.

BACKGROUND A number of patients with neurally mediated syncope (NMS) have isolated QRS complexes of very low voltage (≤0.3 mV) in the frontal plane leads on the 12-lead electrocardiogram (ECG). HYPOTHESIS The aim of this study was to assess the importance of QRS voltage in predicting response to tilt-table testing (TTT) in patients with suspected NMS. METHODS We included 216 patients (age: 49 ± 20 years, 103 men) with suspected NMS who had either a positive or negative response to TTT (n = 91 TTT+, and n = 125 TTT-). The QRS voltage was measured in mV on 12-lead ECGs performed within 3 days of the TTT. The lowest QRS voltage (QRSmin), as well as the voltage in each of the 12 leads was also determined. RESULTS Very low voltage (QRSmin ≤ 0.3 mV) in the frontal leads was significantly more prevalent in the TTT+ group than in the TTT- group (74 vs 22%, respectively; P < .001). Patients in the TTT+ group had significantly lower QRSmin when compared to patients in the TTT- group. QRSmin predicted a positive tilt-table test in a multivariate model that also included patient gender, height, history of presyncope, QRS duration, and left ventricular end-diastolic diameter indexed to height. ROC analysis showed that QRSmin of ≥0.3 mV discriminated between TTT+ and TTT- patients with a sensitivity of 78% and specificity of 68%. CONCLUSION Isolated very low QRS voltage in the frontal leads predicts a positive response to TTT in patients with suspected NMS.

Introduction: We have previously demonstrated that isolated very low QRS voltage (VLV defined as ≤0.3mV) in the frontal leads on the electrocardiogram (ECG; Figure A), as well as flat QRS loops in the frontal plane on ECG-derived vectorcardiograms (VCG; Figure B) predict recurrence of neurally mediated syncope (NMS). This phenomenon is possibly related to a specific ventricular geometry and activation pattern. Hypothesis: The aim of this study was to attempt to incorporate these novel ECG and VCG risk factors for recurrence of syncope into a prognostic risk score. Methods: We included 215 patients (age 48±20years), with NMS and a median of 3 syncopal episodes. The patients were followed for a median of 10 months (IQR 4-20). To weigh the relative importance of the prognostic risk factors identified in multivariate Cox regression analysis we attributed a score of 1 point for HR 1.5-1.99, 2 points for HR 2.0-2.49, and 3 points for HR ≥ 2.5. The total risk score, was divided into three categories: low risk (0-2), intermediate risk (3-5) and high risk (≥6). Results: The multivariate analysis identified history of ≥ 2 syncopal events (HR 3.85, 95%CI 1.62-9.14), left ventricular end-diastolic diameter of < 39mm by echocardiography (HR 1.94, 95%CI 1.00-3.82), isolated VLV QRS in frontal leads (HR 2.60, 95%CI 1.37-4.86) and flat QRS VCG loops in frontal plane (HR 2.23, 95%CI 1.24-3.99) as independent predictors for NMS recurrence (all P < 0.05). The actuarial total syncope recurrence rate at 1 year was 54.6% (95%CI 38.2-72.6) in the high-risk score category, 25.3% (95%CI 16.8-37.1) in the intermediate risk category, and 6.2% (95%CI 2.2-16.2) in the low-risk category (log rank test P Conclusions: The risk of recurrence of NMS could be stratified using a risk score that incorporates novel ECG and VCG parameters in addition to more established clinical and echocardiographic variables.

Introduction: Oral and intravenous (IV) flecainide are recommended as first line therapy for pharmacological cardioversion of recent-onset atrial fibrillation (AF) in patients without known relevant structural heart disease. In the present open-label, dose-escalation study, the feasibility of using flecainide acetate inhalation solution (FlecIH) for acute conversion of recent-onset AF to sinus rhythm (SR) was evaluated. Hypothesis: We hypothesized that FlecIH quickly gives rise to plasma concentrations sufficient to rapidly restore SR in patients with recent-onset AF. Methods: Patients (n=95) with symptomatic AF (for ≤ 48 hours) were enrolled and self-administered FlecIH using a breath-actuated nebulizer (30 mg [n=10], 60 mg [n=20], 90 mg [n=21], 120 mg [n=17], and 120 mg in a formulation containing saccharin [n=27]). Blood samples were collected for flecainide plasma concentrations, electrocardiograms were obtained, cardiac rhythm with a 4-hour Holter and vital signs were monitored, and adverse events (AEs) were recorded. Patients who did not convert to SR were offered alternative treatment per the investigator’s discretion. Results: Conversion rates increased with dose and maximum plasma concentrations (C max ) of flecainide. At the highest dose, 45% of patients converted to normal SR. Patients with C max > 300 ng/mL had a conversion rate of 53% whereas those with C max < 200 ng/mL had a conversion rate of 33%. The median time to conversion was 3.5 min after FlecIH administration. AEs were typically mild and transient. Commonly reported AEs associated with inhalation of flecainide included: cough, throat pain, and throat irritation; at the highest dose with the formulation containing saccharin, these AEs were reported for 37%, 11%, and 4% of patients, respectively. Cardiac AEs consistent with those observed with oral and IV flecainide and considered serious were uncommon and included 2 post-conversion pauses and 1 bradycardia, and 1 atrial flutter with 1:1 atrioventricular conduction; none required treatment and all resolved without sequelae. Conclusions: FlecIH was well tolerated. Inhalation of FlecIH at the 120 mg dose yielded therapeutic plasma levels and conversion rates within the range reported for oral and IV administration.

Background Atrial fibrillation (AF) is common and bears a major clinical impact in patients with hypertrophic cardiomyopathy (HCM). We aimed to investigate the use and real‐world safety of catheter ablation for AF in patients with HCM. Methods and Results We drew data from the US National Inpatient Sample to identify cases of AF ablation in HCM patients between 2003 and 2015. Sociodemographic and clinical data were collected, and incidence of catheter ablation complications, mortality, and length of stay were analyzed, including trends between the early (2003–2008) and later (2009–2015) study years. Among a weighted total of 1563 catheter ablation cases in patients with HCM, the median age was 62 (interquartile range, 52–72), 832 (53.2%) were male, and 1150 (73.6%) were white. The average annual volume of AF ablations in patients with HCM doubled between the early and the later study period (79–156). At least 1 complication occurred in 16.1% of cases, and the in‐hospital mortality rate was 1%. Cardiac and pericardial complications declined from 8.8% to 2.3% and from 2.8% to 0.9%, respectively, between the early and the later study years ( P Conclusions Despite some decline in procedural complications over the years, catheter ablation for AF is still associated with a relatively high periprocedural morbidity and even mortality in patients with HCM. This emphasizes the importance of careful clinical consideration, by an experienced electrophysiologist, in referring patients with HCM for an AF ablation.

Background Delivery of hydrogels to the heart is a promising strategy for mitigating the detrimental impact of myocardial infarction ( MI ). Challenges associated with the in vivo delivery of currently available hydrogels have limited clinical translation of this technology. Gelatin methacryloyl (Gel MA ) bioadhesive hydrogel could address many of the limitations of available hydrogels. The goal of this proof‐of‐concept study was to evaluate the cardioprotective potential of Gel MA in a mouse model of MI . Methods and Results The physical properties of Gel MA bioadhesive hydrogel were optimized in vitro. Impact of Gel MA bioadhesive hydrogel on post‐ MI recovery was then assessed in vivo. In 20 mice, Gel MA bioadhesive hydrogel was applied to the epicardial surface of the heart at the time of experimental MI . An additional 20 mice underwent MI but received no Gel MA bioadhesive hydrogel. Survival rates were compared for Gel MA ‐treated and untreated mice. Left ventricular function was assessed 3 weeks after experimental MI with transthoracic echocardiography. Left ventricular scar burden was measured with postmortem morphometric analysis. Survival rates at 3 weeks post‐ MI were 89% for Gel MA ‐treated mice and 50% for untreated mice ( P =0.011). Left ventricular contractile function was better in Gel MA ‐treated than untreated mice (fractional shortening 37% versus 26%, P MA ‐treated mice was lower than in untreated mice (6% versus 22%, P =0.017). Conclusions Epicardial Gel MA bioadhesive application at the time of experimental MI was performed safely and was associated with significantly improved post‐ MI survival compared with control animals. In addition, Gel MA treatment was associated with significantly better preservation of left ventricular function and reduced scar burden.

Catheter ablation and antiarrhythmic drugs (AADs) are the most common rhythm-control strategies for atrial fibrillation (AF). Data comparing the rate of stroke and cardiovascular events between the treatment strategies are limited. Therefore, this observational study uses claims data to compare rate of cardiovascular hospitalization and stroke for patients with AF treated with ablation or AADs. Patients in the MarketScan dataset with AF between January 2010 and December 2014 were categorized in the ablation group if an atrial catheter ablation was performed, or in the AAD group if a relevant AAD was prescribed for AF but no ablation was performed. One year of history was required, and the index event was selected as the most recent ablation or AAD prescription closest to January 1, 2013. A 2:1 propensity score match was performed for age, gender, co-morbidities, and total medical cost in the year before index event. Outcomes included thromboembolic event (ischemic stroke, transient ischemic attack, or systemic embolism) and all cardiovascular hospitalizations. Of the 164,639 patients in the AAD group, 29,456 were matched to the 14,728 ablation patients. There were no significant differences in age (64 ± 10 in both groups), gender (58% male), or CHA2DS2-VASc score (3.2 ± 1.3). Risk of hospitalization with primary diagnosis of thromboembolic event was 41% greater in the AADs group (p

We investigated the rates and reasons for crossover to alternative treatment strategies and its impact on mortality in patients who were enrolled in the Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) trial. Over a mean follow-up period of 3.5 years, 842 patients underwent crossover to the alternative treatment arms in AFFIRM. The rate of crossover from rhythm to rate control (594/2,033, 29.2%) was more frequent than the rate of crossover from rate to rhythm control (248/2,027, 12.2%, P < 0.0001). The leading reasons for crossover from rhythm to rate control were failure to achieve or maintain sinus rhythm (272/594, 45.8%) and intolerable adverse effects (122/594, 20.5%). In comparison, the major reasons for crossover from rate to rhythm control were failure to control atrial fibrillation symptoms (159/248, 64.1%) and intolerable adverse effects (9/248, 3.6%). This difference in crossover pattern was statistically significant (P < 0.0001). There was a significantly decreased risk of all-cause mortality (adjusted HR: 0.61, 95% CI: 0.48-0.78, P < 0.0001) and cardiac mortality (adjusted hazard ratio [HR]: 0.61, 95% confidence interval [CI]: 0.43-0.88, P = 0.008) in the subgroup of patients who crossed over from rhythm to rate control as compared to those who continued in rhythm control. There was a nonsignificant trend toward decreased all-cause (adjusted HR: 0.76, 95% CI: 0.53-1.10, P = 0.14) and cardiac mortality (adjusted HR: 0.70, 95% CI: 0.42-1.18, P = 0.18) in patients who crossed over from rate to rhythm control as compared to those who continued rate control.

There are limited studies on the safety and efficacy of remote magnetic navigation (RMN) versus manual navigation (MAN) in ventricular tachycardia (VT) ablation. A comprehensive literature search was performed using the keywords VT ablation, stereotaxis, RMN and MAN in Pubmed, Ebsco, Web of Science, Cochrane, and Google scholar databases. The analysis included seven studies (one randomized, three prospective observational, and three retrospective) including 779 patients [both structural heart disease (SHD) and idiopathic VT] comparing RMN (N = 433) and MAN (N = 339) in VT ablation. The primary end point of long-term VT recurrence was significantly lower with RMN (OR 0.61, 95% CI 0.44–0.85, p = 0.003) compared with MAN. Other end points of acute procedural success (OR 2.13, 95% CI 1.40–3.23, p = 0.0004) was significantly higher with RMN compared with MAN. Fluoroscopy [mean difference −10.42, 95% CI −12.7 to −8.1, p

Aims Cardiac resynchronization therapy (CRT) device implantation has been shown to reduce morbidity and mortality in selected patients with heart failure. We sought to investigate the utilization and in-hospital complications of cardiac resynchronization therapy defibrillator (CRT-D) and pacemaker (CRT-P) implantations in the United States from 2003 to 2013. Methods and results Patients receiving CRT-D or CRT-P were identified in the National Inpatient Sample database (NIS), using the International Classification of Diseases-Ninth Revision-Clinical Modification procedure codes. Annual implantation rates, patient demographics, co-morbidities, in-hospital complications, and length of stay were analysed. From 2003 to 2013, an estimated total of 439 010 (95% CI: 406 723–471 296) inpatient CRT implantations were performed in the U.S. The median age of patients was 72 and 71% were male. Overall, 6.1% had at least one complication. During the study period, comorbidity index and overall complication rate increased (P = 0.002 and P = 0.01, respectively). Mortality and length of stay showed no significant trend. Predictors of complications included: age 65 and older, female sex (OR: 1.19; 95% CI: 1.12–1.27), Deyo–Charlson Comorbidity Index, and elective admission (OR: 0.61; 95% CI: 0.57–0.66). Conclusion From 2003 to 2013, the severity of comorbid conditions increased and a rising trend was observed in the rate of periprocedural complications among patients undergoing CRT in the United States. In-hospital mortality and length of stay showed no uniform trend.

AF-mediated cardiomyopathy (AMC) is an important reversible cause of heart failure that is likely underdiagnosed in today’s clinical practice. AMC describes AF either as the sole cause for ventricular dysfunction or exacerbating ventricular dysfunction in patients with existing cardiomyopathy or heart failure. Studies suggest that irreversible ventricular and atrial remodeling can occur in AMC, making timely diagnosis and intervention critical to optimize clinical outcome. Clinical correlation between AF onset/burden and progression of cardiomyopathy/heart failure symptoms provides strong evidence for the diagnosis of AMC. Cardiac MRI, continuous cardiac monitoring, and biomarkers are important diagnostic tools. From the therapeutic standpoint, early data suggest that AF ablation may improve long-term outcomes in AMC patients compared with medical rate and rhythm control. Patients with more AF burden and less severe underlying structural heart disease are more likely to experience left ventricle function recovery with successful AF ablation. Despite recent advances, significant knowledge gaps exist in our understanding of the epidemiology, mechanisms, diagnosis, management strategies, and prognosis of AMC.

Atrial fibrillation (AF) is the most common sustained arrhythmia and is associated with substantial morbidity and impairment of quality of life. Restoration and maintenance of normal sinus rhythm is a desirable goal for many patients with AF; however, this strategy is limited by the relatively small number of antiarrhythmic drugs (AADs) available for AF rhythm control. Although it is recommended in current medical guidelines as first-line therapy for patients without structural heart disease, the use of flecainide has been curtailed since the completion of the Cardiac Arrhythmia Suppression Trial. In clinical trials and real-world use, flecainide has proven to be more effective than other AADs for the acute termination of recent onset AF. Flecainide is also moderately effective and, with the exception of amiodarone, equivalent to other AADs for the chronic suppression of paroxysmal and persistent AF. In patients without structural heart disease, flecainide has been demonstrated to be safe and well tolerated relative to other AADs. Despite this favorable profile, flecainide is underutilized, likely due to a perceived risk of ventricular proarrhythmia, a concern that has not been borne out in patients without underlying structural heart disease. Guidelines for administration and use of flecainide are summarized in this review.

AIMS The TactiCath Contact Force Ablation Catheter Study for Atrial Fibrillation (TOCCASTAR) clinical trial compared clinical outcomes using a contact force (CF) sensing ablation catheter (TactiCath) with a catheter that lacked CF measurement. This analysis links recorded events in the TOCCASTAR study and a large claims database, IBM MarketScan®, to determine the economic impact of using CF sensing during atrial fibrillation (AF) ablation. METHODS AND RESULTS Clinical events including repeat ablation, use of antiarrhythmic drugs, hospitalization, perforation, pericarditis, pneumothorax, pulmonary edema, pulmonary vein stenosis, tamponade, and vascular access complications were adjudicated in the year after ablation. CF was characterized as optimal if greater than or equal to 90% lesion was performed with greater than or equal to 10 g of CF. A probabilistic 1:1 linkage was created for subjects in MarketScan® with the same events in the year after ablation, and the cost was evaluated over 10 000 iterations. Of the 279 subjects in TOCCASTAR, 145 were ablated using CF (57% with optimal CF), and 134 were ablated without CF. In the MarketScan® cohort, 9811 subjects who underwent AF ablation were used to determine events and costs. For subjects ablated with optimal CF, total cost was $19 271 ± 3705 in the year after ablation. For ablation lacking CF measurement, cost was $22 673 ± 3079 (difference of $3402, P

Background During atrial fibrillation (AF), a high rate of myocyte activation causes cellular stress and initiates the process of atrial remodeling, which further promotes persistence of AF. Although heat shock proteins (HSPs) have been shown to prevent atrial remodeling and suppress the occurrence of AF in cellular and animal experimental models, increased levels of HSP-60 have been observed in patients with postoperative AF, likely reflecting a response to cellular stress. To better understand the role of HSP-60 in relation to AF, we examined the association of HSP-60 levels in relation to the future development of AF in the Multi-Ethnic Study of Atherosclerosis (MESA). Methods MESA is a cohort study that recruited 6,814 participants aged 45-84 years and free of known cardiovascular disease at baseline (2000-2002) from six field centers. We investigated 983 participants, selected at random from the total cohort, who had HSP-60 measured and were free of AF at baseline. We tested the association of HSP-60 levels with the incidence of AF using multivariate Cox models after adjustment for demographics, clinical characteristics, and biomarkers. Results During an average of 10.6 years of follow-up, 77 participants developed AF. We did not observe a significant association between the log-transformed HSP-60 levels and development of AF on either unadjusted or multivariate analysis (adjusted hazard ratio: 1.02 per unit difference on natural log scale, 95% confidence interval: 0.77-1.34 ln (ng/mL). Conclusion Contrary to the findings from the preclinical studies, which demonstrated an important role of HSP-60 in the pathogenesis of AF, we did not observe a significant association between HSP-60 and occurrence of AF.

Atrial fibrillation is associated with cognitive impairment ranging from mild to overt dementia, and this association is independent of clinical stroke and multiple shared risk factors. Whether the use of the novel anticoagulants will offer greater protection than warfarin remains to be determined. Rate control strategies may improve brain perfusion and memory but this has not been studied in a randomized controlled trial. Overall, this is a novel field that requires multiple observational studies with long-term follow-up and large-scale randomized controlled trials with accurate neurocognitive testing and brain imaging to ultimately define effective preventive strategies and treatment options.

The study was prompted by our observation that some patients with neurally mediated syncope (NMS) have an isolated QRS complex, of very low voltage (≤0.3 mV cutoff), in 1 of the frontal leads on the 12-lead electrocardiogram.To prospectively evaluate whether the presence of isolated very low voltage (VLV) predicts recurrence of NMS.We included 205 patients (aged 50 ± 17 years) with a median of 3 syncopal episodes. Tilt testing was performed in all patients and was positive in 87 (42%). The patients were followed for a median of 14 months.VLV in frontal leads was present in 92 patients (45%). During the follow-up period 60 patients experienced recurrence of syncope. The actuarial total syncope recurrence rate at 1 year was 32% (95% confidence interval [CI 23%-44%) in patients with isolated VLV in frontal plane leads, and 14% (95% CI 8%-24%) in patients without VLV (log-rank test P.0001). The significant relationship between the presence of isolated VLV in the frontal leads and syncope recurrence was retained in Cox multivariate analysis that included the history of presyncope and syncope as well as the left ventricular end-diastolic diameter. The presence of isolated VLV in frontal leads was associated with a 3-fold increase of the risk of recurrent syncope.Isolated very low QRS voltage in the frontal leads predicts recurrence of NMS independent of clinical factors that predict recurrence of syncope in such patients. This phenomenon may help generate new diagnostic tools and insights into the pathogenesis of NMS.

Prevention of Phrenic Injury Using Imaging Introduction Phrenic nerve (PN) injury is one of the major complications of pulmonary vein isolation (PVI). Pace mapping for PN capture is routinely used to identify areas with high risk for injury along the anterior border of the right pulmonary veins (PVs). Our aim was to evaluate the feasibility of using preprocedural imaging to identify areas where no PN capture is possible along the anterior border of the right PVs, thus avoiding the need for pace mapping during PVI. Methods and Results It was hypothesized that PN capture along the anterior border of the right PVs does not occur in the area where the right and left atria overlap. Three-dimensional segmentation of both atria was performed on preprocedural magnetic resonance and computed tomography angiograms in 40 patients before undergoing PVI. The area of overlap between the right and left atria was delineated. Image registration was performed during the procedure. Using pacing, regions with and without PN capture were marked along the anterior border of the right PVs. A total of 361 points were tested for PN stimulation (9 ± 4 points/patient). PN capture occurred in 97 out of the 189 points (51%) in the area with no overlap between the right and left atria. No PN capture occurred in the area of overlap (172 points, P< 0.001). Conclusion Delineation of the area of overlap between the right and left atria derived from preprocedural imaging reliably identifies regions where PN pace capture does not occur. Testing for PN stimulation before ablation may not be necessary in these regions.

Outcome of Idiopathic Ventricular Fibrillation Background The long-term outcome of the patients with idiopathic ventricular fibrillation (IVF) is not well known. Methods and Results Relevant studies published through May 21, 2014 were searched and identified in the MEDLINE, PsycINFO, Cochrane Library, CINAHL, and EMBASE databases and a hand search of article references was also performed. Random-effect models were used for pooling proportions of mortality and recurrent events. Twenty-three studies were included with a total of 639 patients (449 males) with a mean age ranging from 33 to 51 years. Eighty percent of patients had received ICD implantation. Over an average of 5.3 years follow-up, 167 patients (31%) experienced a recurrence of ventricular arrhythmic events (proportion, 0.29 [95% CI 0.21–0.38]). Moreover, 17 patients (3.1%) died among all studies (proportion, 0.01 [95% CI 0.00–0.04]). No association was found between the induction of sustained ventricular tachycardia or ventricular fibrillation at baseline electrophysiological study and risk of recurrent ventricular arrhythmias (risk difference: 0.12 [95% CI, 0.08–0.32]). Conclusions In patients with IVF, this meta-analysis revealed an estimated recurrent event rate of 31% and a pooled mortality rate of 3.1% during an average of 5 years follow-up. The results of baseline electrophysiological studies are not predictive of future ventricular arrhythmias.

Visually Guided PV Isolation Introduction Visually guided laser balloon (VGLB) ablation is unique in that the operator delivers ablative energy under direct visual guidance. In this multicenter study, we sought to determine the feasibility, efficacy, and safety of performing pulmonary vein isolation (PVI) using this VGLB. Methods Patients with symptomatic, drug-refractory paroxysmal atrial fibrillation (AF) underwent PVI using the VGLB with the majority of operators conducting their first-ever clinical VGLB cases. The primary effectiveness endpoint was defined as freedom from treatment failure that included: Occurrence of symptomatic AF episodes ≥1 minutes beyond the 90-day blanking, the inability to isolate 1 superior and 2 total PVs, occurrence of left atrial flutter or atrial tachycardia, or left atrial ablation/surgery during follow-up. Results A total of 86 patients (mean age 56 ± 10 years, 67% male) were treated with the VGLB at 10 US centers. Mean fluoroscopy, ablation, and procedure times were 39.8 ± 24.3 minutes, 205.2 ± 61.7 minutes, and 253.5 ± 71.3 minutes, respectively. Acute PVI was achieved in 314/323 (97.2%) of targeted PVs. Of 84 patients completing follow-up, the primary effectiveness endpoint was achieved in 50 (60%) patients. Freedom from symptomatic or asymptomatic AF was 61%. The primary adverse event rate was 16.3% (8.1% pericarditis, phrenic nerve injury 5.8%, and cardiac tamponade 3.5%). There were no cerebrovascular events, atrioesophageal fistulas, or significant PV stenosis. Conclusions This multicenter study of operators in the early stage of the learning curve demonstrates that PVI can be achieved with the VGLB with a reasonable safety profile and an efficacy similar to radiofrequency ablation.

Obstructive sleep apnea (OSA) is increasingly recognized as an important risk factor for arrhythmogenesis. Epidemiological and clinical studies have suggested a strong association between OSA and atrial fibrillation (AF). With the increasing global epidemic of obesity, the incidence of OSA is also expected to rise. Various mechanisms mediated through adverse electrical and structural changes have been proposed to explain the increased risk of AF in patients with OSA. Multiple studies have also observed a greater risk of AF recurrence after cardioversion and catheter ablation (CA) in the patients with untreated OSA. The epidemiological and pathophysiological associations between OSA and AF have significant implications on the treatment outcomes of rhythm-control strategies for AF. Adequate screening and optimal management of OSA are of key importance to help improve the clinical outcomes following cardioversion and CA. In this review, we sought to describe the role of various mechanisms by which OSA mediates the pathogenesis of AF and contributes to adverse outcomes following CA.

Background Transcatheter aortic valve replacement (TAVR) has emerged as an alternative treatment for patients with symptomatic aortic stenosis who are at high risk for surgical aortic valve replacement. The development of conduction abnormalities is a major complication in the postprocedural period of TAVR. Objectives The objective of this study was to investigate the development of postprocedural conduction abnormalities and the requirement of permanent pacemaker (PPM) implantation in patients undergoing TAVR. Methods Data from 137 consecutive patients who underwent TAVR (Edwards SAPIEN valve, Edwards Lifesciences, Irvine, CA, USA) between June 2008 and October 2012 were reviewed. Patients with prior history of PPM (n = 27) were excluded. The role of various predictors for pacemaker implantation after TAVR, including the valve index (calculated as [valve size/left ventricular outflow tract diameter] × 100) was investigated. Results A total of 31/110 (28.2%) patients required implantation of a PPM after TAVR. The median time to implantation of a PPM was 5 days after the procedure. The development of postprocedural complete heart block was the most common indication for implantation of a PPM (16/31; 51.6%). On multivariate analysis, the presence of preexisting right bundle branch block (RBBB) was found to be a strong predictor of PPM implantation after TAVR (adjusted odds ratio: 4.87; 95% confidence interval: 1.29–18.46, P = 0.020). Using the receiver operated curve analysis, a cut-off value of valve index of 128 was found to be a strong predictor for PPM implantation with a sensitivity of 73% and specificity of 61% (c statistic = 0.68). Conclusions This study identified the presence of prior RBBB and a valve index of 128 as important risk factors for PPM implantation after TAVR. A larger implanted valve size relative to left ventricular outflow tract diameter leads to a greater compression of the intrinsic conduction system, increasing the need for pacemaker placement.

AF Ablation in Pulmonary Vein Stumps Background Pulmonary vein isolation (PVI) of the remnant pulmonary vein (PV) stumps in pneumonectomy patients has not been well characterized. Methods This is a multicenter observational study of patients with a remnant PV stump after pneumonectomy. Consecutive patients with a history of pneumonectomy and who had undergone RF ablation for drug refractory AF were identified from the AF database at the participating institutions. Results There were 15 patients in whom pneumonectomy was performed, for resection of tumors in 10, infection in 4, and bullae in 1 patient and who underwent RF ablation for AF. The mean age was 63 ± 7 years. The stumps were from the right lower PV in 5, left upper PV in 5, left lower PV in 3, and right upper PV in 2 patients. All the PV stumps were electrically active with PV potentials and 9 (60%) of them had triggered activity. PVI was performed in 14 and focal isolation in 1 patient. At 1-year follow-up, 80% were free of AF, off of antiarrhythmic medications. Conclusion PV stumps in AF patients with previous pneumonectomy are electrically active and are frequently the sites of active firing. Isolation of these PV stumps can be accomplished safely and effectively using catheter ablation with no practical concern for PV stenosis or compromising PV stump integrity.

Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia in adults, associated with significant morbidity, increased mortality, and rising health-care costs. Simple and available tools for the accurate detection of arrhythmia recurrence in patients after electrical cardioversion (CV) or ablation procedures for AF can help to guide therapeutic decisions. We conducted a prospective, single-center study to evaluate the accuracy of Cardiio Rhythm Mobile Application (CRMA) for AF detection. Patients >18 years of age who were scheduled for elective CV for AF were enrolled in the study. CRMA finger pulse recordings, utilizing an iPhone camera, were obtained before (pre-CV) and after (post-CV) the CV. The findings were validated against surface electrocardiograms. Ninety-eight patients (75.5% men), mean age of 67.7 ± 10.5 years, were enrolled. No electrocardiogram for validation was available in 1 case. Pre-CV CRMA readings were analyzed in 97 of the 98 patients. Post-CV CRMA readings were analyzed for 92 of 93 patients who underwent CV. One patient left before the recording was obtained. The Cardiio Rhythm Mobile Application correctly identified 94 of 101 AF recordings (93.1%) as AF and 80 of 88 non-AF recordings (90.1%) as non-AF. The sensitivity was 93.1% (95% confidence interval [CI] = 86.9% to 97.2%) and the specificity was 90.9% (95% CI = 82.9% to 96.0%). The positive predictive value was 92.2% (95% CI = 85.8% to 95.8%) and the negative predictive value was 92.0% (95% CI = 94.8% to 95.9%). In conclusion, the CRMA demonstrates promising potential in accurate detection and discrimination of AF from normal sinus rhythm in patients with a history of AF.

This article discusses how ventricular tachycardia ablation should be used, discusses which patients may derive benefit from this treatment, and highlights the best means of implementing it.

Atrial fibrillation (AF) is the most common cardiac arrhythmia and is associated with a substantial risk of stroke and mortality. Strokes in patients with AF are associated with a greater disability and poorer outcomes than strokes in patients in sinus rhythm. Patients with AF are at increased risk of bleeding, especially if they use anticoagulant therapy. Recent research in the field of anticoagulation has led to development of new anticoagulants for stroke prevention in addition to antiplatelet agents and warfarin. This review discusses the role of AF as a risk factor for stroke and evaluates the role of various schemes for predicting the risk of stroke and bleeding in patients with AF.

OBJECTIVE To evaluate the association between selective serotonin reuptake inhibitors (SSRIs) and corrected QT interval (QTc) prolongation via meta-analysis of prospective studies. DATA SOURCES PubMed/MEDLINE database (January 1, 1975-August 15, 2012), with additional reports identified using hand searches of reference lists of relevant articles. Key words searched were QT, torsades de pointes, and sudden cardiac death, combined with antidepressants, citalopram, escitalopram, fluoxetine, sertraline, paroxetine, and fluvoxamine. English-, Spanish-, and German-language articles were included. STUDY SELECTION Two reviewers independently identified prospective controlled studies in adults that reported data related to QTc intervals prior to and following treatment with SSRIs. DATA EXTRACTION AND SYNTHESIS Three reviewers independently extracted study-level data including population characteristics, method of QTc measurement and treatment and outcome data. Two independent reviewers critiqued study quality. Publication bias was assessed visually using a funnel plot and quantitatively. Heterogeneity was measured using Cochran Q statistic. RESULTS Sixteen articles (with 25 distinct data subsets) involving 4,292 patients were included. SSRIs were associated with a dose-dependent increase in QTc interval compared to placebo (+6.10 milliseconds; 95% CI, 3.47-8.73; P < .001). Tricyclic antidepressants (TCAs) were associated with a significantly greater QTc increase than SSRIs (TCA prolongation, 7.05 milliseconds; 95% CI, 3.84-10.27 greater than SSRIs; P < .001). With respect to specific SSRI agents, citalopram was associated with significantly greater QTc prolongation than sertraline, paroxetine, and fluvoxamine. CONCLUSIONS SSRIs were associated with a modest but statistically significant increase in the QTc interval, although to a lesser extent than TCAs; this finding was not limited to any single study. Citalopram was associated with more QTc prolongation than most other SSRIs.

Background— Cardiac tamponade is the most dramatic complication observed during atrial fibrillation (AF) ablation and the leading cause of procedure-related mortality. Female sex is a known risk factor for complications during AF ablation; however, it is unknown whether women have a higher risk of tamponade. Methods and Results— A systematic Medline search was used to locate academic electrophysiological centers that reported cases of tamponade occurring during AF ablation. Centers were asked to provide information on cases of acute tamponade according to sex and their mode of management including any case of related mortality. Nineteen electrophysiological centers provided information on 34 943 ablation procedures involving 25 261 (72%) men. Overall, 289 (0.9%) cases of tamponade were reported: 120 (1.24%) in women and 169 (0.67%) in men (odds ratio, 1.83; P Conclusions— Tamponade during AF ablation procedures is relatively rare. Women have an ≈2-fold higher risk for developing this complication. The risk of tamponade among women decreases substantially in high-volume centers. Surgical backup and acute management skills for treating tamponade are important in centers performing AF ablation.

Background— Early recurrence of atrial fibrillation (ERAF) is common after radiofrequency catheter ablation for AF. We sought to determine the incidence and prognostic significance of ERAF after cryoballoon ablation. Moreover, the benefit of early reablation for ERAF after cryoballoon ablation is undetermined. Methods and Results— The Sustained Treatment of Paroxysmal Atrial Fibrillation (STOP AF) trial randomized 245 patients with paroxysmal AF to medical therapy versus cryoballoon-based pulmonary vein ablation. Patients were followed for 12 months. ERAF was defined as any recurrence of AF >30 seconds during the first 3 months of follow-up. Late recurrence (LR) was defined as any recurrence of AF >30 seconds between 3 and 12 months. Of the 163 patients randomized to cryoablation, 84 patients experienced ERAF (51.5%). The only significant factor associated with ERAF was male sex (hazard ratio [HR], 2.18; 95% confidence interval [CI], 1.03–4.61; P =0.041). LR was observed in 41 patients (25.1%), and was significantly related to ERAF (55.6% LR with ERAF versus 12.7% without ERAF; P P P =0.002). Conclusions— ERAF after cryoballoon ablation occurs in ≈50% of patients and is strongly associated with LR. Early reablation for ERAF is associated with excellent long-term freedom from recurrent AF.

Objectives This study sought to assess the safety and effectiveness of a novel cryoballoon ablation technology designed to achieve single-delivery pulmonary vein (PV) isolation. Background Standard radiofrequency ablation is effective in eliminating atrial fibrillation (AF) but requires multiple lesion delivery at the risk of significant complications. Methods Patients with documented symptomatic paroxysmal AF and previously failed therapy with ≥1 membrane active antiarrhythmic drug underwent 2:1 randomization to either cryoballoon ablation (n = 163) or drug therapy (n = 82). A 90-day blanking period allowed for optimization of antiarrhythmic drug therapy and reablation if necessary. Effectiveness of the cryoablation procedure versus drug therapy was determined at 12 months. Results Patients had highly symptomatic AF (78% paroxysmal, 22% early persistent) and experienced failure of at least one antiarrhythmic drug. Cryoablation produced acute isolation of three or more PVs in 98.2% and all four PVs in 97.6% of patients. PVs isolation was achieved with the balloon catheter alone in 83%. At 12 months, treatment success was 69.9% (114 of 163) of cryoblation patients compared with 7.3% of antiarrhythmic drug patients (absolute difference, 62.6% [p 75% reduction in PV area during 12 months of follow-up. Twenty-nine of 259 procedures (11.2%) were associated with phrenic nerve palsy as determined by radiographic screening; 25 of these had resolved by 12 months. Cryoablation patients had significantly improved symptoms at 12 months. Conclusions The STOP AF trial demonstrated that cryoballoon ablation is a safe and effective alternative to antiarrhythmic medication for the treatment of patients with symptomatic paroxysmal AF, for whom at least one antiarrhythmic drug has failed, with risks within accepted standards for ablation therapy. (A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation [Stop AF]; NCT00523978 )

Patients with cancer in the United States are estimated to have a suicide incidence that is approximately twice that of the general population. Patients with bone and soft tissue cancer often have physical impairments and activity limitations develop that reduce their quality of life, which may put them at high risk for depression, anxiety, and suicidal ideation. To our knowledge, there have been no large studies determining incidence of suicide among patients with bone and soft tissue cancer; this information might allow screening of certain high-risk groups. To determine (1) the incidence of suicide in patients with bone and soft tissue cancer, (2) whether the incidence of suicide is greater in patients with bone and soft tissue cancer than it is in the general US population, and (3) any demographic and tumor characteristics associated with increased suicide incidence. A retrospective analysis of the Surveillance, Epidemiology, and End Results (SEER) program was performed. A total of 23,620 patients with primary bone and soft tissue cancer were identified in this database from 1973 and 2013. Patients with a cause of death listed as “suicide and self-inflicted injury” were considered to have committed suicide and suicide incidences were determined for different demographic and tumor characteristics in this subset of patients. Patient data for age, gender, race, marital status, year of diagnosis, primary cancer site, cancer stage, course of treatment, and survival time were collected and analyzed. The incidence of suicide in patients with bone and soft tissue sarcoma was compared with the age-, gender-, and race-adjusted incidence of suicide in the general US population from 1970 to 2013 available from the National Center for Health Statistics through the SEER Program. The overall suicide incidence in this population was 32 per 100,000 person-years, which was higher than the age-, race-, and gender-adjusted US general population suicide incidence of 13 per 100,000 person-years. When compared with the incidence of suicide in matched subgroups of the general US population, a higher suicide incidence was observed in men (standardized mortality ratio [SMR], 2.49; 95% CI, 1.92–3.22; p < 0.001), patients of white race (SMR, 2.68; 95% CI, 1.94–3.56; p < 0.001), patients 21 to 30 years old (SMR, 4.40; 95% CI, 3.44–5.54; p < 0.001) and 61 to 70 years old (SMR, 3.27; 95% CI, 2.54–4.18; p < 0.001), patients with cancer of the vertebral column (SMR, 2.88; 95% CI, 2.13–3.83; p < 0.001) and pelvic bones (SMR, 2.75; 95% CI, 2.00–3.65; p < 0.001), and patients within the first 5 years of cancer diagnosis (SMR, 10.8; 95% CI, 9.19–12.61; p < 0.001). With identification of these characteristics that are associated with higher incidence of suicide, physicians should consider screening patients possessing these traits. By identifying at-risk patients, we can hope to reduce the incidence of suicide in this population by providing the treatment that these patients need. Further research must be done to determine how best to screen these patients and to identify the best interventions to reduce suicide incidence. Level III, prognostic study.

Mimicking ST-segment elevation myocardial infarction upon presentation, acute nonrheumatic streptococcal myocarditis is a treatable etiology of myocarditis which has only been infrequently reported.Patients were identified through a retrospective query of electronic medical records over a 17-year period (January 1994 to December 2010). We describe a case series of acute nonrheumatic streptococcal myocarditis complicating pharyngitis in young adults.Nine patients were identified; 89% were male, patients had an average age of 28.6 years, and 56% and 22% had confirmed group A and group G streptococcus, respectively. Latency from pharyngitis to chest pain averaged 3.1±1.1 days. No patients met the revised Jones criteria for acute rheumatic fever. All 9 patients (100%) presented with ST-segment elevations on electrocardiography and elevated cardiac biomarkers. Average peak creatine kinase was 934 U/L (normal400 U/L), creatine kinase-MB was 82 ng/mL (normal6.9 ng/mL), and troponin T was 2.30 ng/mL (normal0.03 ng/mL). Six patients underwent coronary angiography, which revealed no obstructive culprit lesions. Cardiac magnetic resonance imaging confirmed myocarditis in 3 patients and was used to document resolution in follow-up for 2 patients. All patients had a complete clinical recovery.Acute nonrheumatic streptococcal myocarditis is an under-recognized and treatable cause of ST-segment elevation and chest pain in young adults with a history of recent pharyngitis. Etiopathology extends beyond Lancefield group A streptococcus and includes group G streptococcal infection. Cardiac magnetic resonance may be useful in confirming the diagnosis and documenting the resolution.

The termination of persistent atrial fibrillation (AF) during catheter ablation has been associated in some, but not all, studies with reduced arrhythmia during clinical follow-up. We sought to determine the rate of persistent AF termination achievable with a stepwise ablation strategy, the predictors of AF termination, and the clinical outcomes associated with termination and nontermination. A total of 143 consecutive patients (age 62 ± 9 years, AF duration 5.7 ± 5.2 years) with persistent and longstanding persistent AF resistant to antiarrhythmic medication who presented in AF for catheter ablation were studied. Ablation was done with a stepwise approach, including pulmonary vein isolation, followed by complex fractionated atrial electrogram ablation and ablation of resultant atrial tachycardias. Clinical follow-up was then performed after a 2-month blanking period to assess arrhythmia recurrence, defined as AF or atrial tachycardia lasting ≥ 30 seconds. AF termination by ablation was achieved in 95 (66%) of the 143 patients. Multivariate predictors of AF termination included longer baseline AF cycle length (p0.001) and smaller left atrial size (p = 0.002). AF termination by ablation was associated with both a lower incidence of arrhythmia recurrence after a single procedure without antiarrhythmic drugs (p = 0.01) and overall clinical success (single or multiple procedures, with or without antiarrhythmic drugs; p = 0.005). On multivariate analysis, the predictors of overall clinical success included AF termination by ablation (p = 0.001), a shorter ablation duration (p = 0.002), younger age (p = 0.02), male gender (p = 0.03), and the presence of hypertension (p = 0.03). In conclusion, among patients with persistent AF, termination of AF by ablation can be achieved in most patients and is associated with reduced recurrence of arrhythmia.

Background— Patients undergoing cardiac resynchronization therapy (CRT) are at high risk for ventricular arrhythmias (VAs), and risk stratification in this population remains poor. Methods and Results— This study followed 269 patients (left ventricular ejection fraction 120 ms; New York Heart Association class III/IV) undergoing CRT with a defibrillator for 553±464 days after CRT with defibrillator implantation to assess for independent predictors of appropriate device therapy for VAs. Baseline medication use, medical comorbidities, and echocardiographic parameters were considered. The 4-year incidence of appropriate device therapy was 36%. A Cox proportional hazard model identified left ventricular end-systolic diameter >61 mm as an independent predictor in the entire population (hazard ratio [HR], 2.66; P =0.001). Those with left ventricular end-systolic diameter >61 mm had a 51% 3-year incidence of VA compared with a 26% incidence among those with a less dilated ventricle ( P =0.001). Among patients with left ventricular end-systolic diameter ≤61 mm, multivariate predictors of appropriate therapy were absence of β-blocker therapy (HR, 6.34; P P P =0.013). Early (P P Conclusions— Among patients with CRT and a defibrillator, left ventricular end-systolic diameter >61 mm is a powerful predictor of VAs, and further risk stratification of those with less dilated ventricles can be achieved based on assessment of ejection fraction, history of sustained VA, and absence of β-blocker therapy.

Background Predictable progression to battery depletion is necessary for device management in patients with pacemakers or implantable cardioverter-defibrillators, particularly in patients who either are pacemaker dependent or have required implantable cardioverter-defibrillator therapies. Objective To determine the incidence and characteristics of unexpected battery depletion in patients implanted with a cardiac resynchronization therapy – defibrillator (CRT-D) device. Methods All patients with a St Jude Atlas+ HF or Atlas II HF CRT-D device implanted between 2004 and 2007 at the Massachusetts General Hospital and the Nashville VA Medical Center (Vanderbilt University) were studied. All patients with early generator depletion (transition of generator voltage above specified elective replacement indicator [ERI] to end of life [EOL] in less than 90 days) were evaluated further. Results Eight cases (mean age 69.6 ± 9 years) with abrupt battery depletion were identified among 191 patients (4.2%) implanted with a St Jude Atlas CRT-D device. The longevity of 8 premature depletion devices was 46.4 ± 10 months (median 45 months). The battery voltage in these 8 devices decreased from a mean of 2.48 ± 0.03 V (above ERI) to 2.3 ± 0.08 V (below ERI) over 33.3 ± 23 days (range 1–59 days; median 38.5 days). One device reached EOL status within 1 day of having battery voltage above ERI and another device within 12 days. Conclusion The incidence of abrupt battery depletion was 4.2% in patients implanted with a St Jude Atlas CRT-D device. No common mechanism has been identified for this failure. Close monitoring of battery voltage and timely generator replacement are required in patients with these devices.

Aims Previous studies have suggested that upstream medical therapy to modulate the renin-angiotensin axis may facilitate left atrial remodelling and thereby prevent new-onset atrial fibrillation (AF). The purpose of this study was to evaluate the association between angiotensin converting enzyme inhibitor (ACEI) and angiotensin receptor blockers (ARB) on new-onset AF in a large cohort of patients with coronary artery disease (CAD). Methods and results This was a population-based study of 28 620 patients, from community-dwelling Medicare beneficiaries who had been hospitalized for acute myocardial infarction or coronary revascularization (1995–2004). All patients, 65 years and older, had a mean follow-up period of upto 3.8 ± 3.0 years. Patients with a history of AF before and during hospitalization were excluded. We compared the incidence of new-onset AF between patients who were ( N = 10 918) and were not ( N = 17 702) prescribed ACEI and/or ARB within 1 month of hospital discharge following cardiac event. New-onset AF within 5 and 10 years was 39.1 and 61.1%, respectively, in patients who received ACEI/ARB, compared 34.9 and 53.6% in patients who did not receive them [unadjusted hazard ratio (HR): 1.16; 95% confidence interval (CI): 1.11, 1.21]. Multivariable analysis adjusting for patient- and hospital-related characteristics indicated that ACEI/ARB use independently had no impact on the risk of developing new-onset AF compared with non-users (adjusted HR: 0.99; 95% CI: 0.94, 1.04). Adjustment for propensity-score and health-seeking behaviours yielded nearly identical results. Conclusion Angiotensin converting enzyme inhibitor/ARB therapy initiated within 1 month after hospital discharge is not associated with a reduction in the risk of new-onset AF after myocardial infarction or coronary revascularization.

Objectives The purpose of this study was to evaluate the feasibility and safety of uninterrupted rivaroxaban therapy during atrial fibrillation (AF) ablation. Background Optimal periprocedural anticoagulation strategy is essential for minimizing bleeding and thromboembolic complications during and after AF ablation. The safety and efficacy of uninterrupted rivaroxaban therapy as a periprocedural anticoagulant for AF ablation are unknown. Methods We performed a multicenter, observational, prospective study of a registry of patients undergoing AF ablation in 8 centers in North America. Patients taking uninterrupted periprocedural rivaroxaban were matched by age, sex, and type of AF with an equal number of patients taking uninterrupted warfarin therapy who were undergoing AF ablation during the same period. Results A total of 642 patients were included in the study, with 321 in each group. Mean age was 63 ± 10 years, with 442 (69%) males and 328 (51%) patients with paroxysmal AF equally distributed between the 2 groups. Patients in the warfarin group had a slightly higher mean HAS- BLED (hypertension, abnormal renal/liver function, stroke, bleeding history or predisposition, labile international normalized ratio, elderly, drugs/alcohol concomitantly) score (1.70 ± 1.0 vs. 1.47 ± 0.9, respectively; p = 0.032). Bleeding and embolic complications occurred in 47 (7.3%) and 2 (0.3%) patients (both had transient ischemic attacks) respectively. There were no differences in the number of major bleeding complications (5 [1.6%] vs. 7 [1.9%], respectively; p = 0.772), minor bleeding complications (16 [5.0%] vs. 19 [5.9%], respectively; p = 0.602), or embolic complications (1 [0.3%] vs. 1 [0.3%], respectively; p = 1.0) between the rivaroxaban and warfarin groups in the first 30 days. Conclusions Uninterrupted rivaroxaban therapy appears to be as safe and efficacious in preventing bleeding and thromboembolic events in patients undergoing AF ablation as uninterrupted warfarin therapy.

Controlling the ventricular rate during both paroxysmal and persistent atrial fibrillation (AF), initially with digitalis preparations and subsequently with β-blockers and calcium channel blockers, has been a mainstay for the management of this arrhythmia for many years. With the advent of a wide range of pharmacological and nonpharmacological approaches for maintaining sinus rhythm, rhythm control strategies have entered widespread clinical use in selected subsets of symptomatic patients. Despite the availability of these rhythm control strategies, however, rate control of AF remains an important and useful approach for a large number of patients, especially those with little or no symptoms from the arrhythmia once the ventricular rate has been controlled. This review discusses the relative risks and benefits of rate versus rhythm control strategies, describes the targets and available methods for rate control, and highlights special considerations for ventricular rate control when cardiac resynchronization therapy (CRT) is used in patients with AF. Among the most important decisions that must be made by a patient and care provider when choosing a treatment plan for AF is the choice between rate and rhythm control. Rate control is typically a simpler strategy than rhythm control, involving the use of generally less toxic medications and fewer medical procedures, although rate control strategies can result in adverse drug side effects and toxicities and, in some cases, may require interventions such as pacemaker implantation and atrioventricular (AV) nodal ablation. Rhythm control strategies typically involve potentially riskier antiarrhythmic medications or invasive procedures such as catheter ablation or surgery, but, when successful, provide the benefits of sinus rhythm. ### Randomized Trials of Rate versus Rhythm Control Several large randomized, controlled clinical trials have been performed to compare the risks and benefits of rate versus pharmacological rhythm control strategies in patients with AF. Among these are the Atrial Fibrillation Follow-Up Investigation of Rhythm Management (AFFIRM), Rate Control Versus …

Aims Current imaging techniques attempt to identify responders to cardiac resynchronization therapy (CRT). However, because CRT response may depend upon several factors, it may be clinically more useful to identify patients for whom CRT would not be beneficial even under optimal conditions. We aimed to determine the negative predictive value of a composite echocardiographic index evaluating atrial-ventricular dyssynchrony (AV-DYS) and intraventricular dyssynchrony. Methods and results Subjects with standard indications for CRT underwent echo before and during the month following device implantation. AV-DYS was defined as a percentage of left ventricular (LV) filling time over the cardiac cycle. AV-DYS, which produces a characteristic rocking of the LV apex, was quantified as the percentage of the cardiac cycle over which tissue Doppler-derived displacement curves of the septal and lateral walls showed discordance. CRT responder status was determined based on the early haemodynamic response to CRT (intra-individual improvement >25% in the Doppler-derived LV d P /d t ). Among 40 patients, optimal cut-points predicting CRT response were 31% for LV apical rocking and 39% for AV-DYS. The presence of either apical rocking >31% or AV-DYS ≤39% had a sensitivity of 95%, specificity of 80%, positive predictive value of 83%, and a negative predictive value of 94% for CRT response. Conclusion After pre-selection of candidates for CRT by QRS duration, application of a simple composite echocardiographic index may exclude patients who would be non-responders to CRT and thus improve the global rate of therapy success.

Background— Electric alternans is a pattern of variation in the shape of ECG waveform that occurs every other beat. In humans, alternation in ventricular repolarization, known as repolarization alternans (RA), has been associated with increased vulnerability to ventricular tachycardia/fibrillation and sudden cardiac death. Methods and Results— This study investigates the spatio-temporal variability of intracardiac RA and its relationship to body surface RA in an acute myocardial ischemia model in swine. We developed a real-time multichannel repolarization signal acquisition, display, and analysis system to record ECG signals from catheters in the right ventricle, coronary sinus, left ventricle, and epicardial surface before and after circumflex coronary artery balloon occlusion. We found that RA is detectable within 4 minutes after the onset ischemia and is most prominently seen during the first half of the repolarization interval. Ischemia-induced RA was detectable on unipolar and bipolar leads (both in near- and far-field configurations) and on body surface leads. Far-field bipolar intracardiac leads were more sensitive for RA detection than body surface leads, with the probability of body surface RA detection increasing as the number of intracardiac leads detecting RA increased, approaching 100% when at least three intracardiac leads detected RA. We developed a novel, clinically applicable intracardiac lead system based on a triangular arrangement of leads spanning the right ventricular and coronary sinus catheters, which provided the highest sensitivity for intracardiac RA detection when compared with any other far-field bipolar sensing configurations. Conclusions— In conclusion, intracardiac alternans, a complex spatio-temporal phenomenon associated with arrhythmia susceptibility and sudden cardiac death, can be reliably detected through a novel triangular right ventricular–coronary sinus lead configuration.

Detailed information regarding the structure and dimensions of the left atrial appendage (LAA) is required to guide implantation of LAA occlusion devices in patients with atrial fibrillation (AF). Currently, this procedure is guided by transesophageal echocardiography (TEE). The objective of this study was to evaluate the accuracy of intracardiac echocardiography (ICE) in assessing LAA dimensions. The LAA anatomy was analyzed in 21 consecutive patients (age 62 ± 9 years, five women, six paroxysmal AF) who underwent catheter ablation for AF. All patients had pre-procedural scans (computed tomography (CT), N = 9; magnetic resonance imaging (MRI), N = 12) of the left atrium (LA). An 8-Fr phased-array ICE catheter was used to obtain images of the LAA. The LAA was visualized with the ICE probe placed sequentially in the right atrium (RA, N = 21 patients), in the coronary sinus (CS, N = 20 patients), and in the LA (N = 21 patients). ICE imaging from the LA showed a LAA ostium diameter of 24 ± 4 mm and a LAA depth of 32 ± 4 mm. There was strong correlation between the measurements by ICE and the values obtained by CT and MRI. The LAA was visualized in all cases from all locations (RA, CS, and LA), but complete visualization of the LAA could not be obtained from the RA and the CS in a significant number of cases, preventing accurate measurements. Imaging of LAA using an ICE probe positioned in the LA results in accurate measurements of LAA dimensions. This imaging modality could potentially be used during implantation of LAA occlusion devices as an alternative to TEE.

Risk of Stroke/TIA in Patients With Atrial Fibrillation. Introduction: Most strokes in patients with atrial fibrillation (AF) arise from thrombus formation in left atrial appendage (LAA). Our aim was to identify LAA features associated with a higher stroke risk in patients with AF using magnetic resonance imaging and angiography (MRI/MRA). Methods: The study included 144 patients with nonvalvular AF who were not receiving warfarin and who underwent MRI/MRA prior to catheter ablation for AF. LAA volume, LAA depth, short and long axes of LAA neck, and numbers of lobes were measured. Results: Of the 144 patients, 18 had a prior stroke or transient ischemic attack (TIA) (13 and 5, respectively). Compared with patients who had no history of stroke/TIA, these patients were older, had higher prevalence of hypertension and hyperlipidemia and had higher LAA volume (22.9 ± 9.6 cm3 vs. 14.5 ± 7.1 cm3, P < 0.001). Their LAA depth (3.76 ± 0.9 cm vs. 3.21 ± 0.8 cm, P = 0.006) and the long and short axes of the LAA neck (3.12 ± 0.7 cm vs. 2.08 ± 0.7 cm, P < 0.001; 2.06 ± 0.5 cm vs. 1.37 ± 0.4 cm, P < 0.001, respectively) were larger. Using stepwise logistic regression model, the only statistically significant multivariable predictors of events were age (OR = 1.21 per year, 95% CI 1.06-1.38, P = 0.004), aspirin use (OR = 0.039, 95% CI 0.005-0.28, P = 0.001), and LAA neck dimensions (short axis × long axis) (OR = 3.59 per cm2, 95% CI 1.93-6.69, P < 0.001). Conclusion: LAA dimensions predict strokes/TIAs in patients with AF. LAA assessment by MRI/MRA can potentially be used as an adjunctive tool for risk stratification for embolic events in AF patients. (J Cardiovasc Electrophysiol, Vol. 22, pp. 10-15, January 2011)