A Randomized Trial of High vs Standard Power Radiofrequency Ablation for Pulmonary Vein Isolation: SHORT-AF.

BACKGROUND: High-power, short duration (HPSD) radiofrequency ablation (RFA) is a commonly used strategy for pulmonary vein isolation (PVI). OBJECTIVES: This study sought to compare HPSD with standard power, standard duration (SPSD) RFA in patients undergoing PVI. METHODS: Patients with paroxysmal or persistent (<1 year) atrial fibrillation (AF) were randomized to HPSD (50 W) or SPSD (25-30 W) RFA to achieve PVI. Outcomes assessed included time to achieve PVI (primary), left atrial dwell time, total procedure time, first-pass isolation, PV reconnection with adenosine, procedure complications including asymptomatic cerebral emboli (ACE), and freedom from atrial arrhythmias. RESULTS: Sixty patients (median age 66 years; 75% male) with paroxysmal (57%) or persistent (43%) AF were randomized to HPSD (n = 29) or SPSD (n = 31). Median time to achieve PVI was shorter with HPSD vs SPSD (87 minutes vs 126 minutes; P = 0.003), as was left atrial dwell time (157 minutes vs 180 minutes; P = 0.04). There were no differences in first-pass isolation (79% vs 76%; P = 0.65) or PV reconnection with adenosine (12% vs 20%; P = 0.26) between groups. At 12 months, recurrent atrial arrhythmias occurred less in the HPSD group compared with the SPSD group (n = 3 of 29 [10%] vs n = 11 of 31 [35%]; HR: 0.26; P = 0.027). There was a trend toward more ACE with HPSD RFA (40% HPSD vs 17% SPSD; P = 0.053). CONCLUSIONS: In patients undergoing AF ablation, HPSD compared with SPSD RFA results in shorter time to achieve PVI, greater freedom from AF at 12 months, and a trend toward increased ACE.

Human Immunodeficiency Virus Infection and Out-of-Hospital Cardiac Arrest.

Patients with human immunodeficiency virus (HIV) infection are at increased risk of cardiovascular disease, but studies on HIV as a risk factor for cardiac arrest in the general population are lacking. We aimed to examine the association of HIV infection with out-of-hospital cardiac arrests (OHCAs). We used the Office of Statewide Health Planning and Development data to evaluate HIV infection as a predictor of OHCA in all California emergency department encounters from 2005 to 2015, adjusting for age, gender, race, income, obesity, smoking, alcohol, substance abuse, hypertension (HTN), diabetes, coronary artery disease, congestive heart failure (CHF), atrial fibrillation, and chronic kidney disease (CKD). We also determined patient characteristics modifying these associations by including interaction terms in multivariable-adjusted models. In 18,542,761 patients (mean age 47 ± 20 years, 53% women, 43,849 with HIV) followed for a median 6.8 years, 133,983 new OHCA events occurred. Incidence rates in patients with HIV were higher than in patients without HIV (1.99 vs 1.16 OHCA events per 1,000-person-years follow-up). After multivariable adjustment, HIV was associated with a 2.5-fold higher risk of OHCA (hazard ratio 2.47, 95% confidence interval 2.29 to 2.66, p <0.001). The risk of OHCA with HIV was disproportionately stronger in younger patients, women, and in those with HTN, CHF, and CKD. In this large prospective study, HIV was associated with a 2.5-fold increased risk of OHCA, with a greater vulnerability to this outcome in patients with HIV who were female or had HTN, CHF, or CKD.

Incident Strokes Among American Indian Individuals With Atrial Fibrillation.

BACKGROUND American Indian individuals experience a relatively high risk for cardiovascular disease and have exhibited a higher risk of stroke compared with other racial and ethnic minorities. Although this population has the highest incidence of atrial fibrillation (AF) compared with other groups, the relationship between AF and nonhemorrhagic stroke among American Indian individuals compared with other groups has not been thoroughly studied. METHODS and RESULTS We used the Healthcare Cost and Utilization Project to evaluate risk of nonhemorrhagic stroke among American Indian individuals, with comparisons to White, Black, Hispanic, and Asian individuals, among all adult California residents receiving care in an emergency department, inpatient hospital unit, or ambulatory surgery setting from 2005 to 2011. Of 16 951 579 patients followed for a median 4.1 years, 105 822 (0.6%) were American Indian. After adjusting for age, sex, income level, insurance payer, hypertension, diabetes mellitus, coronary artery disease, congestive heart failure, cardiac surgery, valvular heart disease, chronic kidney disease, smoking, obstructive sleep apnea, pulmonary disease, and alcohol use, American Indian individuals with AF exhibited the highest risk of nonhemorrhagic stroke when compared with either non-American Indian individuals with AF (hazard ratio, 1.38; 95% CI, 1.23-1.55; P<0.0001) or to each race and ethnicity with AF. American Indian individuals also experienced the highest overall risk for stroke, with no evidence that AF disproportionately heightened that risk in interaction analyses. CONCLUSIONS American Indian individuals experienced the highest risk of nonhemorrhagic stroke, whether in the presence or absence of AF. Our findings likely suggest an opportunity to further study, if not immediately address, guideline-adherent anticoagulation prescribing patterns among American Indian individuals with AF.

Comparison of remote magnetic navigation ablation and manual ablation of idiopathic ventricular arrhythmia after failed manual ablation.

PURPOSE: Catheter ablation for idiopathic ventricular arrhythmia (VA) is effective and safe, but efficacy is frequently limited due to an epicardial origin and difficult anatomy. The remote magnetic navigation (RMN) catheter has a flexible catheter design allowing access to difficult anatomy. We describe the efficacy of the RMN for ablation of idiopathic VA after failed manual ablation. METHODS: Among 235 patients with idiopathic VA referred for catheter ablation, we identified 51 patients who were referred for repeat ablation after a failed manual ablation. We analyzed the clinical characteristics, including the successful ablation site and findings at electrophysiology study, in repeat procedures conducted using RMN as compared with manual ablation. Among these patients, 22 (43 %) underwent repeat ablation with the RMN and 29 (57 %) underwent repeat ablation with a manual ablation. RESULTS: Overall, successful ablation rate was significantly higher using RMN as compared with manual ablation (91 vs. 69 %, P = 0.02). Fluoroscopy time in the RMN was 17 ± 12 min as compared with 43 ± 18 min in the manual ablation (P = 0.009). Successful ablation rate in the posterior right ventricular outflow tract (RVOT) plus posterior-tricuspid annulus was higher with RMN as compared with manual ablation (92 vs. 50 %, P = 0.03). Neither groups exhibited any major complications. CONCLUSIONS: The RMN is more effective in selected patients with recurrent idiopathic VA after failed manual ablation and is associated with less fluoroscopy time. The RMN catheters have a flexible design enabling them to access otherwise difficult anatomy including the posterior tricuspid annulus and posterior RVOT.

Effect of left ventricular dysfunction and viral load on risk of sudden cardiac death in patients with human immunodeficiency virus.

Human immunodeficiency virus (HIV)-infected patients are disproportionately affected by cardiovascular disease and sudden cardiac death (SCD). Whether left ventricular (LV) dysfunction predicts SCD in those with HIV is unknown. We sought to determine the impact of LV dysfunction on SCD in patients with HIV. We previously characterized all SCDs and acquired immunodeficiency syndrome (AIDS) deaths in 2,860 consecutive patients in a public HIV clinic from 2000 to 2009. Transthoracic echocardiograms (TTEs) performed during the study period were identified. The effect of ejection fraction (EF), diastolic dysfunction, pulmonary artery pressure, and LV mass on SCD and AIDS death were evaluated: 423 patients had at least 1 TTE; 13 SCDs and 55 AIDS deaths had at least 1 TTE. In the propensity-adjusted analysis, EF 30% to 39% and EF<30% predicted SCD (hazard ratio [HR] 9.5, 95% confidence interval [CI] 1.7 to 53.3, p=0.01 and HR 38.5, 95% CI 7.6 to 195.0, p<0.001, respectively) but not AIDS death. Diastolic dysfunction also predicted SCD (HR 14.8, 95% CI 4.0 to 55.4, p<0.001) but not AIDS death, even after adjusting for EF. The association between EF<40% and SCD was greater in subjects with detectable versus undetectable HIV RNA (adjusted HR 11.7, 95% CI 2.9 to 47.2, p=0.001 vs HR 2.7, 95% CI 0.3 to 27.6, p=0.41; p=0.07 for interaction). In conclusion, LV systolic dysfunction and diastolic dysfunction predict SCD but not AIDS death in a large HIV cohort, with greater effect in those with detectable HIV RNA. Further investigation is needed to thoroughly evaluate the effect of low EF and HIV factors on SCD incidence and the potential benefit of implantable cardioverter-defibrillator therapy in this high-risk population.

Association of CASQ2 polymorphisms with sudden cardiac arrest and heart failure in patients with coronary artery disease.

BACKGROUND: Abnormal calcium handling plays a crucial role in arrhythmias, sudden cardiac arrest (SCA), and congestive heart failure (CHF). Calsequestrin 2 (CASQ2) mutations affect calcium release and initiate malignant ventricular arrhythmias (VAs) and SCA syndromes. Common single nucleotide polymorphisms (SNPs) in CASQ2 may be associated with SCA in patients with coronary artery disease (CAD). OBJECTIVE: The purpose of this study was to examine the association of common CASQ2 SNPs with the risk of SCA in patients with CAD. METHODS: CASQ2 SNPs (n = 14) were genotyped and analyzed in a case control study comparing 114 patients with CAD and SCA due to VA to 311 CAD controls without VA or SCA. RESULTS: Multivariate logistic regression adjusting for age and CHF status identified an association between rs7521023 with SCA (odds ratio [OR] 2.72, 95% confidence interval [CI] 1.44-5.13, P = .002). The substantial impact of CHF on SCA in the model (OR 26.6, 95% CI 13.40-52.70, P <.001) led us to further examine the relationship between CHF, SCA, and CASQ2 SNPs. We identified 2 CASQ2 variants (rs7521023: OR 0.4, 95% CI 0.25-0.76, P = .003; rs6684209: OR 19.8, 95% CI 3.63-108.2, P <.001) associated with CHF after adjusting for SCA, age, gender, and hypertension. CONCLUSION: We observed association between a CASQ2 polymorphism and SCA due to VA in patients with CAD adjusting for CHF and independent associations between CASQ2 SNPs and CHF adjusting for SCA. Further investigation in independent cohorts is needed to confirm these findings.

Predictors of fluoroscopy time and procedural failure during biventricular device implantation.

Biventricular device implantation with the insertion of a transvenous left ventricular (LV) lead can be challenging. The aim of this study was to identify predictors of procedural difficulty measured by fluoroscopy time and predictors of LV lead implantation failure. A single-center, retrospective study of 272 consecutive patients who underwent biventricular device implantation from 2004 to 2011 was conducted. Multivariate linear regression was used to assess predictors of fluoroscopy time and logistic regression to identify predictors of LV lead implant failure. The median fluoroscopy time was 36.1 minutes (interquartile range 24.2 to 51.6). After multivariate adjustment, independent predictors of longer fluoroscopy time included a right-sided approach (21.8 minutes longer, 95% confidence interval [CI] 6.8 to 36.9, p = 0.005), previous congenital heart disease surgery (64.6 minutes longer, 95% CI 30.2 to 99.0, p <0.001), and previous failed attempt (30.3 minutes longer, 95% CI 6.0 to 54.5, p = 0.015). Predictors of shorter fluoroscopy time included an LV lead upgrade (7.5 minutes shorter, 95% CI 0.6 to 14.4, p = 0.033), electrophysiology fellow experience (5.4 minutes shorter/year, 95% CI 0.1 to 10.7, p = 0.047), and attending physician experience (1.4 minutes shorter/year, 95% CI 0.01 to 2.9, p = 0.049). Failed implantation occurred in 8% of patients (22 of 272); inability to cannulate the coronary sinus and absent or atretic coronary sinus veins were the most common reasons (8 of 22 failed implants each). A previous failed attempt was the only significant predictor of LV lead implantation failure (odds ratio 33.5, 95% CI 3.2 to 352.6, p = 0.003). In conclusion, 6 patient and operator characteristics predicted LV lead implantation difficulty measured by fluoroscopy time. LV lead implantation failed in 8% of cases, predicted only by a previous failed attempt.

Plasma BIN1 correlates with heart failure and predicts arrhythmia in patients with arrhythmogenic right ventricular cardiomyopathy.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a disorder involving diseased cardiac muscle. Bridging integrator 1 (BIN1) is a membrane-associated protein important to cardiomyocyte homeostasis and is downregulated in cardiomyopathy. We hypothesized that BIN1 could be released into the circulation and that blood-available BIN1 can provide useful data on the cardiac status of patients whose hearts are failing secondary to ARVC. OBJECTIVE: To determine whether plasma BIN1 levels can be used to measure disease severity in patients with ARVC. METHODS: We performed a retrospective cohort study of 24 patients with ARVC. Plasma BIN1 levels were assessed for their ability to correlate with cardiac functional status and predict ventricular arrhythmias. RESULTS: Mean plasma BIN1 levels were decreased in patients with ARVC with heart failure (15 ± 7 vs 60 ± 17 in patients without heart failure, P <.05; the plasma BIN1 level was 60 ± 10 in non-ARVC normal controls). BIN1 levels correlated inversely with number of previous ventricular arrhythmia (R = -.47; P <.05), and low BIN1 levels correctly classified patients with advanced heart failure or ventricular arrhythmia (receiver operator curve area under the curve of 0.88 ± 0.07). Low BIN1 levels also predicted future ventricular arrhythmias (receiver operator curve area under the curve of 0.89 ± 0.09). In a stratified analysis, BIN1 levels could predict future arrhythmias in patients without severe heart failure (n = 20) with an accuracy of 82%. In the 7 patients with ARVC with serial blood samples, all of whom had evidence of disease progression during follow-up, plasma BIN1 levels decreased significantly (a decrease of 63%; P <.05). CONCLUSIONS: Plasma BIN1 level seems to correlate with cardiac functional status and the presence or absence of sustained ventricular arrhythmias in a small cohort of patients with ARVC and can predict future ventricular arrhythmias.

Intracardiac and extracardiac markers of inflammation during atrial fibrillation.

BACKGROUND: A decrease in inflammation after cure of atrial arrhythmias suggests that such arrhythmias are proinflammatory, and lower inflammatory marker levels in the coronary sinus suggest that atrial arrhythmias result in intracardiac appropriation of inflammatory cytokines. OBJECTIVE: The purpose of this study was to investigate the effect of atrial fibrillation on inflammatory markers drawn from intracardiac and extracardiac chambers. METHODS: We performed a case-control study of 167 AF patients and 207 controls. Blood from intracardiac and extracardiac sites was obtained from a subset of patients undergoing curative AF ablation (n = 46). RESULTS: No significant differences in C-reactive protein (CRP) or interleukin-6 (IL-6) levels were seen between patients with and those without a history of AF. Both levels were significantly higher when blood was drawn during AF than during sinus rhythm: median CRP 3.1 mg/dL (interquartile range [IQR] 1.0-6.0) versus 1.7 mg/dL (IQR 0.7-3.9, P = .0005); median IL-6 2.3 ng/mL (IQR 1.5-3.9) versus 1.5 ng/mL (IQR 0.7-2.5, P = .007). This finding persisted after adjusting for potential confounders. AF ablation patients in AF exhibited a positive median left atrial minus coronary sinus gradient CRP (0.3 mg/dL, IQR -0.03-1.1), whereas those in sinus rhythm had a negative median left atrial minus coronary sinus gradient CRP (-0.2, IQR -0.8-[-0.02], P = .01). Femoral artery minus femoral vein gradients in AF versus sinus rhythm did not show any differences. CONCLUSION: AF at the time of the blood draw, rather than a history of AF, was independently associated with inflammation. Differences in transcardiac gradients suggest that AF results in sequestration of inflammatory cytokines in the heart.

Association of TGFBR2 polymorphism with risk of sudden cardiac arrest in patients with coronary artery disease.

BACKGROUND: Transforming growth factor ss (TGFss) signaling has been shown to promote myocardial fibrosis and remodeling with coronary artery disease (CAD), and previous studies show a major role for fibrosis in the initiation of malignant ventricular arrhythmias (VA) and sudden cardiac arrest (SCA). Common single nucleotide polymorphisms (SNPs) in TGFss pathway genes may be associated with SCA. OBJECTIVE: We examined the association of common SNPs among 12 candidate genes in the TGFss pathway with the risk of SCA. METHODS: SNPs (n = 617) were genotyped in a case-control study comparing 89 patients with CAD and SCA caused by VA to 520 healthy control subjects. RESULTS: Nineteen SNPs among 5 genes (TGFB2, TGFBR2, SMAD1, SMAD3, SMAD6) were associated with SCA after adjustment for age and sex. After permutation analysis to account for multiple testing, a single SNP in TGFBR2 (rs9838682) was associated with SCA (odds ratio: 1.66, 95% confidence interval: 1.08 to 2.54, P = .02). CONCLUSION: We show an association between a common TGFBR2 polymorphism and risk of SCA caused by VA in the setting of CAD. If validated, these findings support the role of genetic variation in TGFss signaling in SCA susceptibility.

Impact of remote magnetic catheter navigation on ablation fluoroscopy and procedure time.

BACKGROUND: Remote magnetic catheter navigation (RCN) is gaining acceptance in clinical cardiac electrophysiology, but details regarding how RCN affects procedure execution are not well characterized. METHODS: From January 1, 2005, to November 30, 2007, 721 cases were retrospectively analyzed and compared. Of these, 127 used RCN and 594 used manual catheter navigation (MCN). Data including procedure time, fluoroscopy time, ablation catheter, procedural success, and complications were extracted from our procedure database and compared between RCN and MCN. RESULTS: RCN use significantly decreased fluoroscopy time for atrial fibrillation (AF) ablation (-29 minutes, P < 0.001), atrioventricular nodal reentrant tachycardia ablation (-14 minutes, P < 0.001), and atrioventricular reentrant tachycardia ablation (-18 minutes, P = 0.045). While RCN significantly increased mean procedure time for AF (+36 minutes, P = 0.003) and atypical atrial flutter cases (+116 minutes, P = 0.016), RCN AF procedure time diminished with increasing number of cases performed. Two cases of tamponade occurred during AF ablation using MCN (2.2%, 2 of 91 cases). No tamponade occurred during all 75 AF ablations with RCN. CONCLUSION: RCN can reduce fluoroscopy time and may reduce complications during catheter ablation. While it may increase total procedure duration, procedure times decrease with increasing operator experience. (PACE 2008; 31:1399-1404).

Common beta-adrenergic receptor polymorphisms are not associated with risk of sudden cardiac death in patients with coronary artery disease.

BACKGROUND: Previous studies suggest that beta-adrenergic receptor (betaAR) single nucleotide polymorphisms (SNPs) are associated with out-of-hospital sudden cardiac death (SCD) and overall mortality, but did not specifically examine risk of ventricular arrhythmias (VA). OBJECTIVE: This study examined the effects of functional SNPs of beta1AR and beta2AR on the risk of VA and SCD in patients with coronary artery disease (CAD). METHODS: beta1AR (Ser49Gly, Arg389Gly) and beta2AR (Gly16Arg, Gln27Glu) SNPs were genotyped in a case-control study comparing 107 patients with CAD and aborted SCD due to VA with 287 CAD control subjects and 101 healthy control subjects. These variants were also examined in the Heart and Estrogen Replacement Study (HERS) cohort of women with CAD followed for SCD (n = 66) and nonfatal VA (NFVA) (n = 33) over 6.8 years. RESULTS: In the case-control study, no statistically significant association was observed for the odds of SCD with any of the SNPs or haplotypes tested. Similarly, HERS revealed null effects for these SNPs and haplotypes in relation to risk of SCD, SCD + NFVA, and all-cause mortality. Point estimates and confidence intervals for risk of SCD associated with beta2AR27 were similar in both populations (Glu27 carriers vs Gln27 homozygotes: adjusted odds ratio 1.23 [95% confidence interval 0.75 to 2.03, P = .41] in the case-control study, and adjusted relative risk (RR) 1.18 [95% confidence interval 0.69 to 2.00, P = .55] in HERS). These null findings trend in the opposite direction and differ from previous published estimates (P = .01 and .07, respectively). CONCLUSION: We did not find an increase in risk of SCD associated with any of these common betaAR polymorphisms.

Markers of inflammation before and after curative ablation of atrial flutter.

BACKGROUND: Atrial arrhythmias are associated with inflammation. The cause and effect of the association are unknown. OBJECTIVE: The purpose of this study was to test the hypothesis that atrial tachyarrhythmias contribute to inflammation. METHODS: We performed a prospective observational study wherein C-reactive protein (CRP) and interleukin-6 (IL-6) levels from the femoral vein and coronary sinus (CS) were compared before curative ablation for atrial flutter (AFL; n = 59) and paroxysmal supraventricular tachycardia (SVT; n = 110). Follow-up levels were obtained at 1 and 6 months. RESULTS: Peripheral levels of both biomarkers were significantly higher in the AFL group. After multivariate adjustment, only those in the AFL group who presented in AFL or atrial fibrillation (AF) had significantly elevated CRP levels (odds ratio 1.26; P = .033). Levels of each marker were similar in the CS and peripheral blood in the SVT group; in the AFL group, both CRP and IL-6 were significantly lower in the CS than in the periphery (P = .0076 and P = .0021, respectively). CRP was significantly lower a median of 47 days after AFL ablation (from a median of 6.28 mg/L to a median of 2.92 mg/L; P = .028) and remained reduced at second follow-up. IL-6 decreased across three time points after AFL ablation (P = .002). No reduction in inflammatory biomarkers was observed after SVT ablation. CONCLUSIONS: CRP and IL-6 levels are elevated in patients presenting in AFL. Given the lower CS values in these patients, their origin appears to be systemic rather than cardiac. Because these levels significantly fall after ablation of AFL, the atrial tachyarrhythmia appears to be the cause (not the effect) of the inflammation.

Sudden cardiac death: epidemiology, mechanisms, and therapy.

Sudden cardiac death is a major public health problem affecting 500,000 patients annually in the United States alone. The major risk factor for sudden cardiac death is the presence of coronary artery disease, usually in the setting of reduced ejection fraction. Globally, the incidence is expected to rise sharply as the prevalence of coronary artery disease and heart failure continue to increase. However, sudden cardiac death is a heterogeneous condition and may be caused by acute ischemia, structural defects, myocardial scar, and/or genetic mutations. Sudden death may occur even in a grossly normal heart. Beta-blockers can reduce the risk of sudden cardiac death, while implantable cardioverter defibrillators are effective at terminating malignant arrhythmias. Ejection fraction remains the major criterion to stratify patients for defibrillator implantation but this strategy alone is insensitive and nonspecific. Novel clinical, electrophysiologic, and genetic markers have been identified that may increase precision in patient selection for primary prevention therapy. This review discusses the epidemiology, mechanisms, etiologies, therapies, treatment guidelines, and future directions in the management of sudden cardiac death.

Repeat transseptal catheterization after ablation for atrial fibrillation.

INTRODUCTION: A substantial number of patients require a second left atrial procedure after ablation for atrial fibrillation (AF), either for left atrial flutter or recurrent AF. The success and complication rates of repeat transseptal catheterization in these patients are unknown. The aim of this study was to determine the difficulty and/or success rates of repeat transseptal catheterization after left atrial ablation for AF. METHODS AND RESULTS: Consecutive patients undergoing repeat left atrial procedures after ablation for AF over a 1-year period were enrolled. Difficulties with, success rates, and complications of the first and second transseptal catheterizations were recorded. Sixteen patients underwent a repeat transseptal catheterization. Of the 4 in whom the first procedure was performed with an ablation catheter across a patent foramen ovale (PFO), 3 required a transseptal puncture for their repeat procedure. The remaining 12 underwent transseptal puncture without difficulty for their first procedure, and, despite the same operators for each patient, the repeat transseptal was noted to be difficult in 5. Of those 5, the transseptal puncture was unsuccessful due to increased interatrial septal thickness in 2 patients. One repeat transseptal attempt was aborted after posterior right atrial puncture with the transseptal needle occurred, attributed to distorted interatrial septal anatomy not observed prior to the first case. CONCLUSIONS: Compared with the first procedure, repeat transseptal catheterization after ablation for AF, whether initially performed across a PFO or via a transseptal puncture, is more difficult, less often successful, and potentially associated with more complications.