Pasquale Santangeli

Does the left atrial appendage morphology correlate with the risk of stroke in patients with atrial fibrillation?: results from a multicenter study.

OBJECTIVES This study investigated the left atrial appendage (LAA) by computed tomography (CT) and magnetic resonance imaging (MRI) to categorize different LAA morphologies and to correlate the morphology with the history of stroke/transient ischemic attack (TIA). BACKGROUND LAA represents one of the major sources of cardiac thrombus formation responsible for TIA/stroke in patients with atrial fibrillation (AF). METHODS We studied 932 patients with drug-refractory AF who were planning to undergo catheter ablation. All patients underwent cardiac CT or MRI of the LAA and were screened for history of TIA/stroke. Four different morphologies were used to categorize LAA: Cactus, Chicken Wing, Windsock, and Cauliflower. RESULTS CT scans of 499 patients and MRI scans of 433 patients were analyzed (age 59 ± 10 years, 79% were male, and 14% had CHADS(2) [Congestive heart failure, hypertension, Age >75, Diabetes mellitus, and prior stroke or transient ischemic attack] score ≥2). The distribution of different LAA morphologies was Cactus (278 [30%]), Chicken Wing (451 [48%]), Windsock (179 [19%]), and Cauliflower (24 [3%]). Of the 932 patients, 78 (8%) had a history of ischemic stroke or TIA. The prevalence of pre-procedure stroke/TIA in Cactus, Chicken Wing, Windsock, and Cauliflower morphologies was 12%, 4%, 10%, and 18%, respectively (p = 0.003). After controlling for CHADS2 score, gender, and AF types in a multivariable logistic model, Chicken Wing morphology was found to be 79% less likely to have a stroke/TIA history (odd ratio: 0.21, 95% confidence interval: 0.05 to 0.91, p = 0.036). In a separate multivariate model, we entered Chicken Wing as the reference group and assessed the likelihood of stroke in other groups in relation to reference. Compared with chicken wing, cactus was 4.08 times (p = 0.046), Windsock was 4.5 times (p = 0.038), and Cauliflower was 8.0 times (p = 0.056) more likely to have had a stroke/TIA. CONCLUSIONS Patients with Chicken Wing LAA morphology are less likely to have an embolic event even after controlling for comorbidities and CHADS2 score. If confirmed, these results could have a relevant impact on the anticoagulation management of patients with a low-intermediate risk for stroke/TIA.

Left Atrial Appendage An Underrecognized Trigger Site of Atrial Fibrillation

Background— Together with pulmonary veins, many extrapulmonary vein areas may be the source of initiation and maintenance of atrial fibrillation. The left atrial appendage (LAA) is an underestimated site of initiation of atrial fibrillation. Here, we report the prevalence of triggers from the LAA and the best strategy for successful ablation. Methods and Results— Nine hundred eighty-seven consecutive patients (29% paroxysmal, 71% nonparoxysmal) undergoing redo catheter ablation for atrial fibrillation were enrolled. Two hundred sixty-six patients (27%) showed firing from the LAA and became the study population. In 86 of 987 patients (8.7%; 5 paroxysmal, 81 nonparoxysmal), the LAA was found to be the only source of arrhythmia with no pulmonary veins or other extrapulmonary vein site reconnection. Ablation was performed either with focal lesion (n=56; group 2) or to achieve LAA isolation by placement of the circular catheter at the ostium of the LAA guided by intracardiac echocardiography (167 patients; group 3). In the remaining patients, LAA firing was not ablated (n=43; group 1). At the 12±3-month follow-up, 32 patients (74%) in group 1 had recurrence compared with 38 (68%) in group 2 and 25 (15%) in group 3 (P<0.001). Conclusions— The LAA appears to be responsible for arrhythmias in 27% of patients presenting for repeat procedures. Isolation of the LAA could achieve freedom from atrial fibrillation in patients presenting for a repeat procedure when arrhythmias initiating from this structure are demonstrated.

Periprocedural Stroke and Management of Major Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation The Impact of Periprocedural Therapeutic International Normalized Ratio

Background— Catheter ablation of atrial fibrillation is associated with the potential risk of periprocedural stroke, which can range between 1% and 5%. We developed a prospective database to evaluate the prevalence of stroke over time and to assess whether the periprocedural anticoagulation strategy and use of open irrigation ablation catheter have resulted in a reduction of this complication. Methods and Results— We collected data from 9 centers performing the same ablation procedure with the same anticoagulation protocol. We divided the patients into 3 groups: ablation with an 8-mm catheter off warfarin (group 1), ablation with an open irrigated catheter off warfarin (group 2), and ablation with an open irrigated catheter on warfarin (group 3). Outcome data on stroke/transient ischemic attack and bleeding complications during and early after the procedures were collected. Of 6454 consecutive patients in the study, 2488 were in group 1, 1348 were in group 2, and 2618 were in group 3. Periprocedural stroke/transient ischemic attack occurred in 27 patients (1.1%) in group 1 and 12 patients (0.9%) in group 2. Despite a higher prevalence of nonparoxysmal atrial fibrillation and more patients with CHADS2 (congestive heart failure, hypertension, age >75 years, diabetes mellitus, and prior stroke or transient ischemic attack) score >2, no stroke/transient ischemic attack was reported in group 3. Complications among groups 1, 2, and 3, including major bleeding (10 [0.4%], 11 [0.8%], and 10 [0.4%], respectively; P>0.05) and pericardial effusion (11 [0.4%], 11 [0.8%], and 12 [0.5%]; P>0.05), were equally distributed. Conclusion— The combination of an open irrigation ablation catheter and periprocedural therapeutic anticoagulation with warfarin may reduce the risk of periprocedural stroke without increasing the risk of pericardial effusion or other bleeding complications.

Periprocedural Stroke and Bleeding Complications in Patients Undergoing Catheter Ablation of Atrial Fibrillation With Different Anticoagulation Management Results From the Role of Coumadin in Preventing Thromboembolism in Atrial Fibrillation (AF) Patients Undergoing Catheter Ablation (COMPARE) Randomized Trial

Background— Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results— This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1–55.6; P<0.001). Conclusion— This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

Endo-epicardial homogenization of the scar versus limited substrate ablation for the treatment of electrical storms in patients with ischemic cardiomyopathy.

OBJECTIVES This study investigated the impact on recurrences of 2 different substrate approaches for the treatment of these arrhythmias. BACKGROUND Catheter ablation of electrical storms (ES) for ventricular arrhythmias (VAs) has shown moderate long-term efficacy in patients with ischemic cardiomyopathy. METHODS Ninety-two consecutive patients (81% male, age 62 ± 13 years) with ischemic cardiomyopathy and ES underwent catheter ablation. Patients were treated either by confining the radiofrequency lesions to the endocardial surface with limited substrate ablation (Group 1, n = 49) or underwent endocardial and epicardial ablation of abnormal potentials within the scar (homogenization of the scar, Group 2, n = 43). Epicardial access was obtained in all Group 2 patients, whereas epicardial ablation was performed in 33% (14) of these patients. RESULTS Mean ejection fraction was 27 ± 5. During a mean follow-up of 25 ± 10 months, the VAs recurrence rate of any ventricular tachycardia (VTs) was 47% (23 of 49 patients) in Group 1 and 19% (8 of 43 patients) in Group 2 (log-rank p = 0.006). One patient in Group 1 and 1 patient in Group 2 died at follow-up for noncardiac reasons. CONCLUSIONS Our study demonstrates that ablation using endo-epicardial homogenization of the scar significantly increases freedom from VAs in ischemic cardiomyopathy patients.

Periprocedural Stroke and Bleeding Complications in Patients undergoing Catheter Ablation of Atrial Fibrillation with Different Anticoagulation Management: Results from the "COMPARE" Randomized Trial

Background— Periprocedural thromboembolic and hemorrhagic events are worrisome complications of catheter ablation for atrial fibrillation (AF). The periprocedural anticoagulation management could play a role in the incidence of these complications. Although ablation procedures performed without warfarin discontinuation seem to be associated with lower thromboembolic risk, no randomized study exists. Methods and Results— This was a prospective, open-label, randomized, parallel-group, multicenter study assessing the role of continuous warfarin therapy in preventing periprocedural thromboembolic and hemorrhagic events after radiofrequency catheter ablation. Patients with CHADS2 score ≥1 were included. Patients were randomly assigned in a 1:1 ratio to the off-warfarin or on-warfarin arm. The incidence of thromboembolic events in the 48 hours after ablation was the primary end point of the study. The study enrolled 1584 patients: 790 assigned to discontinue warfarin (group 1) and 794 assigned to continuous warfarin (group 2). No statistical difference in baseline characteristics was observed. There were 39 thromboembolic events (3.7% strokes [n=29] and 1.3% transient ischemic attacks [n=10]) in group 1: two events (0.87%) in patients with paroxysmal AF, 4 (2.3%) in patients with persistent AF, and 33 (8.5%) in patients with long-standing persistent AF. Only 2 strokes (0.25%) in patients with long-standing persistent AF were observed in group 2 (P<0.001). Warfarin discontinuation emerged as a strong predictor of periprocedural thromboembolism (odds ratio, 13; 95% confidence interval, 3.1–55.6; P<0.001). Conclusion— This is the first randomized study showing that performing catheter ablation of AF without warfarin discontinuation reduces the occurrence of periprocedural stroke and minor bleeding complications compared with bridging with low-molecular-weight heparin. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT01006876.

Meta-analysis: Age and Effectiveness of Prophylactic Implantable Cardioverter-Defibrillators

BACKGROUND Implantable cardioverter-defibrillators (ICDs) for the primary prevention of sudden cardiac death have been proven effective in several clinical trials. PURPOSE To summarize evidence about the effectiveness of ICDs versus standard medical therapy for the primary prevention of sudden cardiac death in different age groups of patients with severe left ventricular dysfunction. DATA SOURCES MEDLINE, Embase, CENTRAL, BioMed Central, Cardiosource, ClinicalTrials.gov, and ISI Web of Science (January 1970 to April 2010) were searched with no language restrictions. STUDY SELECTION Two independent reviewers screened titles and abstracts to identify randomized, controlled trials of prophylactic ICD versus medical therapy in patients with severe left ventricular dysfunction that provided data about mortality outcomes for different age groups. DATA EXTRACTION Two independent reviewers assessed risk for bias of trials and extracted patient and study characteristics and hazard ratios (HRs) relevant to all-cause mortality. DATA SYNTHESIS Five trials (MADIT-II, DEFINITE, DINAMIT, SCD-HeFT, and IRIS) that enrolled 5783 patients (44% were elderly) were included. The primary analysis, which excluded the 2 trials enrolling patients early after acute myocardial infarction (DINAMIT and IRIS), found that prophylactic ICD therapy reduced mortality in younger patients (HR, 0.65 [95% CI, 0.50 to 0.83]; P < 0.001). A smaller survival benefit was found in elderly patients (HR, 0.75 [95% CI, 0.61 to 0.91]) that was not confirmed when MADIT-II patients older than 70 years were excluded or when data from DINAMIT and IRIS were included [corrected]. LIMITATIONS Four potentially eligible trials were not included in the meta-analysis because mortality data by age group were not available. Adjustment for differences in comorbid conditions and medical therapies among patients enrolled in the trials was not possible. CONCLUSION Available data suggest that prophylactic ICD therapy may be less beneficial for elderly patients with severe left ventricular dysfunction than for younger patients [corrected]. PRIMARY FUNDING SOURCE None.

General anesthesia reduces the prevalence of pulmonary vein reconnection during repeat ablation when compared with conscious sedation: Results from a randomized study

BACKGROUND Radiofrequency catheter ablation of atrial fibrillation can be performed under general anesthesia or conscious sedation at the physicians preference. OBJECTIVE We randomized a series of consecutive patients with paroxysmal atrial fibrillation (AF) undergoing radiofrequency catheter ablation to either general anesthesia or conscious sedation to assess differences in pulmonary vein (PV) reconnection during redo procedures and impact on success rate. METHODS A total of 257 consecutive patients with paroxysmal AF undergoing AF ablation were enrolled and randomized to either conscious sedation with fentanyl or midazolam (128 patients, group 1) and general anesthesia (129 patients, group 2). In all patients, a high dosage of isoproterenol up to 30 μg/min was used to disclose PV reconnection or extra PV firings. RESULTS Baseline clinical characteristics were not significantly different between the 2 groups. At 17 ± 8 month follow-up after the first ablation, 88 (69%) patients in group 1 were free of atrial arrhythmias off all antiarrhythmic drugs (AAD), as compared with 114 (88%) in group 2 (log-rank P <.001). All patients with recurrence had a second procedure. At the repeat procedure, 42% (66 of 158) of PVs in group 1 had recovered PV conduction, compared with 19% (11 of 57) in group 2 (P = .003). Compared with group 1, group 2 had a significantly shorter fluoroscopy time (53 ± 9 min vs. 84 ± 21 min, P <.001) and procedure time (2.4 ± 1.4 h vs. 3.6 ± 1.1 h, P <.001). CONCLUSION The use of general anesthesia is associated with higher cure rate with a single procedure, and it seems to reduce the prevalence of PV reconnection observed at the time of repeat ablation.

Gender differences in clinical outcome and primary prevention defibrillator benefit in patients with severe left ventricular dysfunction: A systematic review and meta-analysis

BACKGROUND Women are underrepresented in primary prevention implantable cardioverter-defibrillator (ICD) trials, and data on the benefit of ICD therapy in this subgroup are controversial. OBJECTIVE The purpose of this study was to better evaluate the benefit of prophylactic ICD in women by performing a meta-analysis of primary prevention ICD trials that assessed gender differences on the end-points of total mortality, appropriate ICD intervention, and survival benefit of ICD compared with placebo. METHODS PubMed, CENTRAL, and other databases were searched in October 2009. Studies were included only if they examined gender differences in the specified end-points, providing the hazard ratio (HR) obtained in multiple Cox regression analyses, and adjusted for all confounding variables. RESULTS We retrieved five studies (MADIT-II, MUSTT, SCD-HeFT, DEFINITE, COMPANION) that enrolled 7,229 patients (22% women) with dilated cardiomyopathy (74% ischemic). Compared to men, women had no significant difference in overall mortality (HR 0.96, 95% confidence interval [CI] 0.67-1.39, P = .84) but experienced significantly less appropriate ICD interventions (HR 0.63, 95% CI 0.49-0.82, P < or =.001). The benefit of ICD on mortality was significantly higher in men (HR 0.67, 95% CI 0.58-0.78, P <.001) but did not reach statistical significance in women (HR 0.78, 95% CI 0.57-1.05, P = .1). CONCLUSION Women enrolled in primary prevention ICD trials have the same mortality compared to men while experiencing significantly less appropriate ICD interventions, thus suggesting a smaller impact of sudden cardiac death on overall mortality in women with dilated cardiomyopathy. These findings may explain the smaller ICD survival benefit among women.

Atrial fibrillation and the risk of incident dementia: A meta-analysis

BACKGROUND The risk of cerebrovascular embolic events with atrial fibrillation (AF) is potentially linked to an increased risk of cognitive decline and dementia. However, epidemiologic studies exploring the association between AF and incident dementia have reported conflicting results. OBJECTIVE The purpose of this study was to perform a meta-analysis of observational studies specifically designed to evaluate the prospective relationship between AF and incident dementia. METHODS We searched PubMed, CENTRAL, BioMedCentral, Embase, Cardiosource, clinicaltrials.gov, and ISI Web of Science (January 1980 to May 2012). No language restriction was applied. Two independent reviewers screened titles and abstracts to identify population-based studies that prospectively evaluated the association between AF and the incidence of dementia in patients not suffering an acute stroke and with normal cognitive function at baseline, providing the hazard ratio (HR) obtained in multiple Cox regression analyses, and adjusted for all confounding variables. Two independent reviewers assessed risk of bias according to the Cochrane Collaboration, and extracted patient and study characteristics and the adjusted HR of incident dementia with its 95% confidence interval (CI) of patients with AF vs those without AF. RESULTS Eight studies with 77,668 patients were included in the analysis. All studies had a prospective observational design and included elderly patients (mean age range 61-84 years) with normal cognitive function at baseline, of whom 11,700 (15%) had AF. After a mean follow-up of 7.7 ± 9.1 years (range 1.8-30 years), 4773 of 73,321 (6.5%) patients developed dementia. Two studies did not report the rates of dementia at follow-up but reported the adjusted HR and were included in the pooled analysis. At pooled analysis adjusted for baseline confounders and covariates, AF was independently associated with increased risk of incident dementia (HR = 1.42 [95% CI 1.17-1.72], P <.001). CONCLUSION AF is independently associated with increased risk of dementia. Patients with AF should be periodically screened for dementia, which should be included among the outcomes assessed in AF treatment trials.