Differences in intraprocedural ACTs with standardized heparin dosing during catheter ablation for atrial fibrillation in patients treated with dabigatran vs. patients on uninterrupted warfarin.

PURPOSE: Effective intraprocedural anticoagulation for catheter ablation for atrial fibrillation is critical to minimize the risk of cerebral thromboembolism. The effect of dabigatran on anticoagulation with heparin during the procedure is unknown. This study compares heparin anticoagulation in patients treated with dabigatran vs. patients on uninterrupted warfarin. METHODS: Seventy-six consecutive patients (24 dabigatran and 52 warfarin) subjected to a standard intraprocedural heparin protocol were included. Heparin administration and rapidity and degree of anticoagulation were compared between the groups. RESULTS: Despite greater administration of heparin (52.5 ± 22.0 vs. 33.2 ± 10.1 units kg(-1) h(-1); p < 0.001), the mean (320.3 ± 19.5 s) and peak (358.8 ± 28.6 s) activated clotting time (ACT) for the dabigatran group were significantly lower than for the warfarin group (mean, 362.9 ± 35.9 and peak, 410.4 ± 49.7; p < 0.001). The time from initial heparin bolus to first ACT of ≥300 s in the dabigatran group was more than twice that observed in the warfarin group (45.0 ± 30.4 vs. 20.9 ± 14.5 min; p < 0.001). The time to first ACT of ≥350 s was similarly prolonged (109.1 ± 60.0 vs. 55.2 ± 51.1 min; p < 0.001) in the dabigatran group, with eight patients (33 %) failing to reach this target. Outcome differences persisted following analysis using linear models and Cox proportional hazard regression with adjustment for propensity scores. CONCLUSION: A standard intraprocedural heparin protocol results in delayed and lower levels of anticoagulation as measured by the ACT for patients treated with dabigatran compared with those on uninterrupted warfarin.

Chronic kidney disease and mortality in implantable cardioverter-defibrillator recipients.

Incidence of sudden cardiac death (SCD) in end-stage renal disease (ESRD) remains high. Limited data is available about whether implantable cardioverter-defibrillators (ICDs) can prevent arrhythmic death in patients with chronic kidney disease (CKD). The purpose of this retrospective study was to determine the impact of CKD on all-cause and sudden cardiac death in ICD recipients. We evaluated 441 consecutive patients who underwent ICD implantation at our center between 1994 and 2002. We found that mortality rate was higher in patients with eGFR <60 mL/min and those with ESRD on hemodialysis (43%, n = 69/162 and 54%, n = 12/22, resp.) than in patients with eGFR >/=60 mL/min (23%, n = 58/257; P < .0005). The SCD rate was also higher in the patients with ESRD (50%) than in CKD patients not on dialysis (10.2%; P < .0005). Mortality rate for single-chamber ICDs was 56.8% in comparison with dual-chamber ICDs (38.1%) and for biventricular ICDs (5.0%) (P < .0005).

Fragmented QRS and mortality risk in patients with left ventricular dysfunction.

BACKGROUND: Fragmented QRS (fQRS) has been shown to predict cardiac events in select patient populations. Whether fQRS improves patient selection for primary prevention patients eligible for implantable cardioverter-defibrillator (ICD) therapy remains unknown. METHODS AND RESULTS: In a prospective, multisite cohort of 842 patients with left ventricular dysfunction (ejection fraction < or =35%) representing both ischemic and nonischemic etiology, the presence of fQRS on ECG was assessed using standardized criteria. The association between fQRS and all-cause and arrhythmic mortality was evaluated overall and stratified by ICD status using multivariable Cox regression models, adjusted for demographic, clinical, and treatment variables. Fragmented QRS was present in 274 (32.5%) patients, and there were 191 (22.7%) deaths during a mean follow-up of 40+/-17 months. Rates of all-cause mortality did not differ between the fQRS+ (19.7%) and fQRS- (24.1%) groups; adjusted hazard ratio, 0.88; 95% confidence interval, 0.63-1.22; P=0.43. Additionally, rates of arrhythmic mortality were similar between the fQRS+ (9.9%) and fQRS- (12.7%) groups: adjusted hazard ratio, 0.77; 95% confidence interval, 0.49-1.31; P=0.38. Subgroup analyses found no association between fQRS and mortality when the cohort was further stratified by ICD status, etiology of left ventricular dysfunction, wide (>/=120 ms) versus narrow (<120 ms) QRS duration, or fQRS myocardial territory. CONCLUSIONS: In this prospective, multisite cohort of primary prevention patients with left ventricular dysfunction, the presence of fQRS on ECG was not associated with a higher risk of either all-cause or arrhythmic mortality. These findings do not provide evidence that fQRS would be effective in risk stratifying primary prevention patients eligible for ICD therapy.

Long- and short-term temporal stability of complex fractionated atrial electrograms in human left atrium during atrial fibrillation.

BACKGROUND: Complex fractionated atrial electrograms (CFAEs) have been reported as targets for catheter ablation of atrial fibrillation (AF). However, the temporal stability of CFAE sites remains poorly defined. METHODS AND RESULTS: The study consisted of two phases. In the initial phase, two automated software algorithms, namely the interval confidence level (ICL) and the average interpotential interval (AIPI) were assessed for their diagnostic accuracy for automated CFAE detection. The AIPI was found to be superior to the ICL, and an AIPI of

Complications of catheter ablation for atrial fibrillation: incidence and predictors.

INTRODUCTION: Pulmonary vein (PV) isolation by catheter ablation is an increasingly used strategy to treat atrial fibrillation (AF). Complication rates from AF ablation reported in different case series vary widely. We conducted a retrospective analysis of 641 consecutive ablation procedures to assess complication rates, temporal trends, and clinical predictors of adverse outcomes. METHODS: All patients (n = 517) undergoing catheter ablation for AF at Johns Hopkins Hospital between February, 2001 and June, 2007 were prospectively enrolled in a database. Data from 641 consecutive procedures were analyzed and complications considered if they occurred within 30 days of ablation. Major complications were defined as those that required intervention, resulted in long-term disability, or prolonged hospitalization. RESULTS: Thirty-two major complications occurred in 641 procedures (5%). Among the patients with major complications, seven had cerebrovascular accident (CVA), eight had tamponade, one had PV occlusion with hemoptysis, and 11 had vascular injury requiring surgical repair and/or transfusion. No periprocedural deaths occurred, and no instances of esophageal injury were seen. Complication rates were higher during the first 100 cases (9.0%) than during the subsequent 541 (4.3%). Major adverse clinical events were associated with age > 70 years (P = 0.007; odds ratio 3.7, 95% confidence interval 1.4-9.6) and female gender (P = 0.014; odds ratio 3.0, 95% confidence interval 1.3-7.2). No other clinical or procedural predictors of complication were identified. CONCLUSIONS: Complication rates from AF ablation remain significant, despite improved techniques and increased awareness of procedural risks. Both advanced age and female gender predict major adverse events, suggesting careful consideration of the risk/benefit profile in these patients prior to ablation.

Impact of heart rhythm status on registration accuracy of the left atrium for catheter ablation of atrial fibrillation.

INTRODUCTION: Registration accuracy is of crucial importance to the successful use of image integration technique to facilitate atrial fibrillation (AF) ablation. It is well known that a patient's heart rhythm can switch from sinus rhythm (SR) to AF or vice versa during an AF ablation procedure. However, the impact of the heart rhythm change on the accuracy of left atrium (LA) registration has not been studied. METHODS: This study included 10 patients who underwent AF ablation. Prior to the ablation procedure, the patients had contrast-enhanced cardiac CT scan obtained during SR (n = 7) or AF (n = 3). Using an image integration system (CartoMerge, Biosense Webster Inc.), LA CT surface reconstruction was registered to the real-time mapping space represented by the LA electroanatomic map. To determine the effect of rhythm change on registration accuracy, LA registration was performed during both SR and AF in each study subject. The distance between the surface of the registered LA CT reconstruction and multiple real-time LA electroanatomic map points (surface-to-point distance) was used as an index for LA registration error. The position error after rhythm change was defined as the surface-to-point distance between the surface of the LA CT reconstruction registered in the initial rhythm and the LA electroanatomic map points sampled during the second rhythm. RESULTS: A total of 90 +/- 12 and 92 +/- 9.5 LA electroanatomic map points were sampled for registration during SR and AF, respectively. No significant difference was found in surface-to-point distance when comparing SR with AF as the underlying rhythm during registration (1.91 +/- 0.24 vs 1.84 +/- 0.38 mm, P = 0.60). The position error after rhythm change was not different from the surface-to-point distance of LA registration conducted during the initial rhythm (2.05 +/- 0.39 vs 1.96 +/- 0.29 mm, P = 0.4). The surface-to-point distance did not differ when comparing LA registration conducted during the same versus different rhythm from that during CT imaging (1.96 +/- 0.29 vs 1.79 +/- 0.32 mm, P = 0.13). CONCLUSIONS: Registration error did not differ between LA registrations conducted during the same versus different rhythm as was present during CT imaging. Rhythm changes between SR and AF did not introduce significant error to the LA registration process for catheter ablation of AF. These findings are reassuring and suggest that reregistration is not needed if a patient's rhythm changes from SR to AF or vice versa during an ablation procedure.

C-reactive protein in cardiovascular risk assessment: a review of the evidence.

C-reactive protein (CRP) is an inflammatory biomarker that is strongly associated with coronary heart disease, inflammation, and the metabolic syndrome. Large-scale prospective cohort trials have shown that measurement of CRP may add predictive accuracy to the Framingham risk score, but interpretation of these data are conflicting. In the primary prevention setting, CRP can be used to reclassify patients in low or intermediate Framingham risk score groups to a higher risk category, thus making them eligible for more intensive pharmacologic interventions.

Automated detection and characterization of complex fractionated atrial electrograms in human left atrium during atrial fibrillation.

BACKGROUND: Complex fractionated atrial electrograms (CFAEs) have been reported as ablative targets for the treatment of atrial fibrillation (AF). However, the process of CFAE identification is highly dependent on the operator's judgment. OBJECTIVE: It is the aim of the study to report our initial experience with a novel software algorithm designed to automatically detect CFAEs. METHODS: Nineteen patients (6 female, 58 +/- 8 years) who underwent catheter ablation of paroxysmal (n = 11) or persistent (n = 8) AF were included in the study. During ongoing AF, 100 +/- 15 left atrial (LA) endocardial locations were sampled under the guidance of integrated electroanatomical mapping with computed tomographic images. Bipolar electrograms recorded throughout the LA were analyzed using custom software that allows for automated detection of CFAEs. Interval confidence level (ICL), defined as the number of intervals between consecutive CFAE complexes during 2.5-second recordings, was used to characterize CFAEs. The CFAE sites with an ICL >/=5 were considered as sites with highly repetitive CFAEs, which are thought to be potential ablation targets. For purposes of analysis, the LA was divided into 6 areas: pulmonary vein (PV) ostia, posterior wall, interatrial septum, roof, mitral annulus area, and appendage. RESULTS: Among a total of 1,904 LA locations sampled in 19 patients, 1,644 (86%) were categorized as CFAE sites, whereas 260 (14%) were categorized as as non-CFAE sites. Thirty-four percent of all CFAE sites were identified as sites with highly repetitive CFAEs. Of these, 24% were located at the interatrial septum, 22% on the posterior wall, 20% at the PV ostia, 18% at the mitral annulus area, 14% on the roof, and 2.7% at the LA appendage. In all patients, highly repetitive CFAE sites were distributed in 4 or more areas of the LA. Persistent AF patients had more highly repetitive CFAE sites on the posterior wall than paroxysmal AF patients (30% +/- 7.3% vs 14% +/- 8.2%, P < .001). There was a strong trend toward more highly repetitive CFAE sites located at the PV ostia in patients with paroxysmal AF compared with persistent AF patients (24% +/- 13% vs 13% +/- 7.7%, P = .05). CONCLUSION: With the use of custom software, CFAE complexes were identified in more than 80% of the LA endocardial locations. LA sites with highly repetitive CFAE sites were located predominately in the septum, posterior wall, and PV ostia. Patients with persistent AF had a different anatomical distribution pattern of highly repetitive CFAE sites from those with paroxysmal AF, with a greater prevalence of highly repetitive CFAEs located on the posterior wall. Further studies are warranted to determine the clinical significance of these findings.

Circumferential ablation with pulmonary vein isolation in permanent atrial fibrillation.

Each of the main approaches to catheter ablation of atrial fibrillation (AF, segmental and circumferential) is associated with limited efficacy in patients with permanent AF. The objective is to report outcomes of circumferential ablation with pulmonary vein (PV) isolation, determined using a circular mapping catheter, in patients with permanent AF and determine relations between the duration of permanent AF and efficacy. The patient population was composed of 41 consecutive patients (34 men; age 58 +/- 11 years) with permanent AF who underwent radiofrequency catheter ablation through circumferential ablation with PV isolation. They were in permanent AF for 2.3 +/- 3.6 years, and 3.4 +/- 2.2 cardioversion procedures and 1.9 +/- 0.8 class I/III antiarrhythmic drugs had failed. After a follow-up of 11 +/- 2 months, the single-procedure success rate was 36% (n = 15) with an additional 12% (n = 5) showing improvement. With repeat procedures in 19%, the success rate was 54% (n = 22) with an additional 12% (n = 5) showing improvement. All patients who underwent repeat ablations had recovered PV conduction. Single-procedure success was higher in patients who were in permanent AF for < or =1 year compared with those in permanent AF for >1 year (50% vs 20%, respectively, p = 0.05). A major complication occurred in 4 patients (8%), including 3 patients with vascular complications and 1 with stroke. In conclusion, study results suggest that circumferential ablation with PV isolation has moderate efficacy in patients with permanent AF. Efficacy is limited in those in continuous AF for >12 months.

Incidence and time course of early recovery of pulmonary vein conduction after catheter ablation of atrial fibrillation.

BACKGROUND: Although it is well recognized that recovery of pulmonary vein (PV) conduction is common among patients who fail atrial fibrillation (AF) ablation, little is known about the precise time course of recurrence. OBJECTIVE: To determine the incidence and time course of early recurrence of conduction after PV isolation during AF ablation. METHODS: The patient population was composed of 14 consecutive patients (9 men [64%]; age 56 +/- 7 years) with AF who underwent radiofrequency catheter ablation via circumferential ablation with PV isolation, determined by a circular mapping catheter. After successful isolation of the PVs, repeat circular electrode recordings from each PV were obtained at 30 and 60 minutes. RESULTS: After complete isolation of all PVs, early PV recurrence was observed in 13 (93%) patients and 26 veins (50%). Seventeen veins (33%) showed a first recurrence at 30 minutes, while nine veins (17%) showed a first recurrence at 60 minutes. CONCLUSION: The results reveal an extremely high rate of early recurrence of PV conduction following AF ablation. It is particularly notable that about one-fifth of the veins remained isolated at 30 minutes, but subsequently developed recurrence between 30 and 60 minutes. Of the veins that showed early recurrence, one-third developed a first recurrence at 60 minutes. These findings suggest that AF ablation procedures should incorporate a 60-minute waiting period after initial isolation in order to detect early recurrence of conduction.

Long-term single procedure efficacy of catheter ablation of atrial fibrillation.

BACKGROUND: Two important limitations of the data regarding the outcomes of catheter ablation of atrial fibrillation (AF) are the short-term follow-up used in most published studies and the lack of single-procedure outcomes. OBJECTIVE: The objective was to report the long-term single-procedure outcomes at our center. MATERIALS AND METHODS: The patient population was comprised of 200 consecutive patients who underwent ablation (133 men; age 56 +/- 11 years). Atrial fibrillation was paroxysmal in 92 (46%). Success was defined as absence of symptomatic AF, off antiarrhythmic drug (AAD) after a single procedure. RESULTS: After a follow-up of 26 +/- 11 months, the single-procedure long-term success rate was 28% with an additional 7% of patients demonstrating improvement. After including repeat procedures in 64 patients, the overall long-term success rate was 41% with 11% demonstrating improvement. Further subgroup analysis of 48 paroxysmal AF patients considered to be optimal candidates for the procedure, revealed a long-term success rate of 69% with an additional 4% demonstrating improvement. A major complication occurred in 7.9% of patients. CONCLUSION: The results reveal that the long-term single-procedure success rate of catheter ablation of AF in a cohort of patients with predominantly non-paroxysmal AF is less than 40%. The inclusion of redo procedures resulted in an improvement in outcomes. A much higher success rate of 69% was achieved in patients with paroxysmal AF considered to be optimal candidates for this procedure. These results make it clear that further advances in the technique of catheter ablation of AF are needed to improve the safety and efficacy of this procedure. In order to be able to compare outcomes of various techniques in differing patient populations, we urge investigators to report long-term single procedure outcomes.

Usefulness of clinical evaluation, troponins, and C-reactive protein in predicting mortality among stable hemodialysis patients.

This study prospectively examined the hypothesis that dividing stable dialysis patients into different clinical subsets by presence or absence of coronary disease equivalent will lead to clearer risk stratification by abnormal troponins and highly sensitive C-reactive protein (hs-CRP). Patients with end-stage renal disease have an annual mortality of 18%. Previous studies have shown that elevated cardiac troponins T and I and hs-CRP predict increased mortality, although these studies have not taken clinical parameters into account. Stable patients with end-stage renal disease (n = 173) were divided into 2 groups: 115 patients with coronary disease equivalent (known coronary or peripheral vascular disease or diabetes mellitus) and 58 patients without it. The 2 groups were then stratified by biomarkers (cardiac troponins T and I and hs-CRP) and followed for 27 months. The primary outcome was all-cause mortality. Patients with coronary disease equivalent had twofold greater annual mortality than those without (20.4% vs 9.8%, p = 0.003). Among patients with coronary disease equivalent, those with elevated troponins had a further increase in the risk for death relative to patients with normal troponins (25% vs 9% with cardiac troponin I elevation, p <0.001; 24% vs 12% with cardiac troponin T elevation, p = 0.04). hs-CRP did not add to the risk stratification of patients with coronary disease equivalent. Conversely, in patients without coronary disease equivalent, neither troponin further predicted the risk for death. In the small subset of patients without coronary disease equivalent who had hs-CRP >or=3 mg/L, mortality was significantly increased (p = 0.01). In conclusion, initial clinical assessment, followed by the addition of biomarkers, can be used to risk-stratify stable patients with end-stage renal disease.

Long-term safety and efficacy of circumferential ablation with pulmonary vein isolation.

BACKGROUND: Each of the two main approaches to catheter ablation of atrial fibrillation (AF, segmental and circumferential) is associated with moderate long-term efficacy. OBJECTIVE: To report the long-term outcomes of a modified technique that combines circumferential ablation with pulmonary vein (PV) isolation, determined by a circular mapping catheter and to determine the relationship between complete PV isolation and long-term efficacy. METHODS: The patient population was composed of 64 consecutive patients (47 men [73%]; age 59 +/- 11 years) with AF who underwent catheter ablation. AF was paroxysmal in 29 (45%) and nonparoxysmal in 35 (55%). Each patient was followed for a minimum of 12 months. RESULTS: After a mean follow-up of 13 +/- 1 months, the long-term single-procedure success rate was 45% (n = 29) with an additional 4% (n = 3) of patients demonstrating improvement. With repeat procedures in 19 patients, the overall long-term success rate was 62% (n = 40) with 9% (n = 6) demonstrating improvement. All the patients who underwent repeat ablations had recovered PV conduction. Incomplete PV isolation was the only independent predictor of failure. A major complication occurred in four (6%) patients, including three patients with vascular complications and one with cardiac tamponade. CONCLUSION: Our results suggest that the long-term single-procedure efficacy of circumferential ablation with PV isolation in a cohort of patients with predominantly nonparoxysmal AF approaches 50%. Repeat procedures involving re-isolation of the PVs result in a significant improvement in outcomes. Complete electrical isolation of the PVs has a significant impact on the long-term efficacy of the procedure.

Initial experience in the use of integrated electroanatomic mapping with three-dimensional MR/CT images to guide catheter ablation of atrial fibrillation.

INTRODUCTION: No prior studies have reported the use of integrated electroanatomic mapping with preacquired magnetic resonance/computed tomographic (MR/CT) images to guide catheter ablation of atrial fibrillation (AF) in a series of patients. METHODS AND RESULTS: Sixteen consecutive patients with drug-refractory AF underwent catheter ablation under the guidance of a three-dimensional (3D) electroanatomic mapping system (Carto, Biosense Webster, Inc., Diamond Bar, CA, USA). Gadolinium-enhanced MR (n = 8) or contrast-enhanced high-resolution CT (n = 8) imaging was performed within 1 day prior to the ablation procedures. Using a novel software package (CartoMerge, Biosense Webster, Inc.), the left atrium (LA) with pulmonary veins (PVs) was segmented and extracted for image registration. The segmented 3D MR/CT LA reconstruction was accurately registered to the real-time mapping space with a combination of landmark registration and surface registration. The registered 3D MR/CT LA reconstruction was successfully used to guide deployment of RF applications encircling the PVs. Upon completion of the circumferential lesions around the PVs, 32% of the PVs were electrically isolated. Guided by a circular mapping catheter, the remaining PVs were disconnected from the LA using a segmental approach. The distance between the surface of the registered 3D MR/CT LA reconstruction and multiple electroanatomic map points was 3.05 +/- 0.41 mm. No complications were observed. CONCLUSIONS: Three-dimensional MR/CT images can be successfully extracted and registered to anatomically guided clinical AF ablations. The display of detailed and accurate anatomic information during the procedure enables tailored RF ablation to individual PV and LA anatomy.

Recurrent acute profound thrombocytopenia related to readministration of eptifibatide.

We describe the case of an 86-year-old woman who presented with unstable angina. She was given heparin and eptifibatide, and she underwent percutaneous coronary intervention (PCI). Shortly thereafter, she developed acute profound thrombocytopenia (6,000 platelets/mm3), which resolved after the discontinuation of heparin and eptifibatide. Four months later, she presented again with unstable angina and underwent PCI. Soon after the procedure, she again developed acute profound thrombocytopenia (2,000 platelets/mm3). To our knowledge, acute profound thrombocytopenia due to eptifibatide treatment in the same patient at two different times has not been reported before.

Should people on aspirin avoid Ibuprofen? A review of the literature.

Aspirin reduces the secondary incidence of myocardial infarction and vascular death, but some people on aspirin sustain a subsequent vascular event, suggesting the phenomenon of aspirin resistance. Based on epidemiologic data, some people have recommended avoiding ibuprofen in patients taking aspirin and suggested that ibuprofen reverses the cardioprotection offered by aspirin. We review the related literature. Although the interaction between aspirin and ibuprofen is pharmacologically plausible as shown by in vivo studies, the clinical implications of this observation are unknown. There are no randomized, controlled trials addressing this particular issue. The data obtained from observational and epidemiologic studies is scanty, conflicting, and limited. Therefore, the advice to avoid ibuprofen in patients taking aspirin to avoid the reversal of cardioprotection offered by aspirin seems premature.