Effect of High-Dose Omega-3 Fatty Acids vs Corn Oil on Major Adverse Cardiovascular Events in Patients at High Cardiovascular Risk: The STRENGTH Randomized Clinical Trial.

Importance: It remains uncertain whether the omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) reduce cardiovascular risk. Objective: To determine the effects on cardiovascular outcomes of a carboxylic acid formulation of EPA and DHA (omega-3 CA) with documented favorable effects on lipid and inflammatory markers in patients with atherogenic dyslipidemia and high cardiovascular risk. Design, Setting, and Participants: A double-blind, randomized, multicenter trial (enrollment October 30, 2014, to June 14, 2017; study termination January 8, 2020; last patient visit May 14, 2020) comparing omega-3 CA with corn oil in statin-treated participants with high cardiovascular risk, hypertriglyceridemia, and low levels of high-density lipoprotein cholesterol (HDL-C). A total of 13 078 patients were randomized at 675 academic and community hospitals in 22 countries in North America, Europe, South America, Asia, Australia, New Zealand, and South Africa. Interventions: Participants were randomized to receive 4 g/d of omega-3 CA (n = 6539) or corn oil, which was intended to serve as an inert comparator (n = 6539), in addition to usual background therapies, including statins. Main Outcomes and Measures: The primary efficacy measure was a composite of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke, coronary revascularization, or unstable angina requiring hospitalization. Results: When 1384 patients had experienced a primary end point event (of a planned 1600 events), the trial was prematurely halted based on an interim analysis that indicated a low probability of clinical benefit of omega-3 CA vs the corn oil comparator. Among the 13 078 treated patients (mean [SD] age, 62.5 [9.0] years; 35% women; 70% with diabetes; median low-density lipoprotein [LDL] cholesterol level, 75.0 mg/dL; median triglycerides level, 240 mg/dL; median HDL-C level, 36 mg/dL; and median high-sensitivity C-reactive protein level, 2.1 mg/L), 12 633 (96.6%) completed the trial with ascertainment of primary end point status. The primary end point occurred in 785 patients (12.0%) treated with omega-3 CA vs 795 (12.2%) treated with corn oil (hazard ratio, 0.99 [95% CI, 0.90-1.09]; P = .84). A greater rate of gastrointestinal adverse events was observed in the omega-3 CA group (24.7%) compared with corn oil-treated patients (14.7%). Conclusions and Relevance: Among statin-treated patients at high cardiovascular risk, the addition of omega-3 CA, compared with corn oil, to usual background therapies resulted in no significant difference in a composite outcome of major adverse cardiovascular events. These findings do not support use of this omega-3 fatty acid formulation to reduce major adverse cardiovascular events in high-risk patients. Trial Registration: ClinicalTrials.gov Identifier: NCT02104817.

Varespladib and cardiovascular events in patients with an acute coronary syndrome: the VISTA-16 randomized clinical trial.

IMPORTANCE: Secretory phospholipase A2 (sPLA2) generates bioactive phospholipid products implicated in atherosclerosis. The sPLA2 inhibitor varespladib has favorable effects on lipid and inflammatory markers; however, its effect on cardiovascular outcomes is unknown. OBJECTIVE: To determine the effects of sPLA2 inhibition with varespladib on cardiovascular outcomes. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial at 362 academic and community hospitals in Europe, Australia, New Zealand, India, and North America of 5145 patients randomized within 96 hours of presentation of an acute coronary syndrome (ACS) to either varespladib (n = 2572) or placebo (n = 2573) with enrollment between June 1, 2010, and March 7, 2012 (study termination on March 9, 2012). INTERVENTIONS: Participants were randomized to receive varespladib (500 mg) or placebo daily for 16 weeks, in addition to atorvastatin and other established therapies. MAIN OUTCOMES AND MEASURES: The primary efficacy measure was a composite of cardiovascular mortality, nonfatal myocardial infarction (MI), nonfatal stroke, or unstable angina with evidence of ischemia requiring hospitalization at 16 weeks. Six-month survival status was also evaluated. RESULTS: At a prespecified interim analysis, including 212 primary end point events, the independent data and safety monitoring board recommended termination of the trial for futility and possible harm. The primary end point occurred in 136 patients (6.1%) treated with varespladib compared with 109 patients (5.1%) treated with placebo (hazard ratio [HR], 1.25; 95% CI, 0.97-1.61; log-rank P = .08). Varespladib was associated with a greater risk of MI (78 [3.4%] vs 47 [2.2%]; HR, 1.66; 95% CI, 1.16-2.39; log-rank P = .005). The composite secondary end point of cardiovascular mortality, MI, and stroke was observed in 107 patients (4.6%) in the varespladib group and 79 patients (3.8%) in the placebo group (HR, 1.36; 95% CI, 1.02-1.82; P = .04). CONCLUSIONS AND RELEVANCE: In patients with recent ACS, varespladib did not reduce the risk of recurrent cardiovascular events and significantly increased the risk of MI. The sPLA2 inhibition with varespladib may be harmful and is not a useful strategy to reduce adverse cardiovascular outcomes after ACS. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01130246.

Effect of aliskiren on progression of coronary disease in patients with prehypertension: the AQUARIUS randomized clinical trial.

IMPORTANCE: Blood pressure reduction and renin-angiotensin-aldosterone system inhibition are targets for treatment of atherosclerosis. The effect of renin inhibition on coronary disease progression has not been investigated. OBJECTIVE: To determine the effects of renin inhibition with aliskiren on progression of coronary atherosclerosis. DESIGN, SETTING, AND PARTICIPANTS: A double-blind, randomized, multicenter trial (Aliskiren Quantitative Atherosclerosis Regression Intravascular Ultrasound Study) comparing aliskiren with placebo in 613 participants with coronary artery disease, systolic blood pressure between 125 and 139 mm Hg (prehypertension range), and 2 additional cardiovascular risk factors conducted at 103 academic and community hospitals in Europe, Australia, and North and South America (enrollment from March 2009 to February 2011; end of follow-up: January 31, 2013). INTERVENTIONS: Participants underwent coronary intravascular ultrasound (IVUS) imaging and were randomized to receive 300 mg of aliskiren (n = 305) or placebo (n = 308) taken orally daily for 104 weeks. Disease progression was measured by repeat IVUS examination after at least 72 weeks of treatment. MAIN OUTCOMES AND MEASURES: The primary efficacy parameter was the change in percent atheroma volume (PAV) from baseline to study completion. Secondary efficacy parameters included the change in normalized total atheroma volume (TAV) and the percentage of participants with atheroma regression. Safety and tolerability were also assessed. RESULTS: Evaluable imaging data were available at baseline and follow-up for 458 participants (74.7%). The primary IVUS efficacy parameter, PAV, did not differ between participants treated with aliskiren (-0.33%; 95% CI, -0.68% to 0.02%) and placebo (0.11%; 95% CI, -0.24% to 0.45%) (between-group difference, -0.43% [95% CI, -0.92% to 0.05%]; P = .08). The secondary IVUS efficacy parameter, TAV, did not differ between participants treated with aliskiren (-4.1 mm3; 95% CI, -6.27 to -1.94 mm3) and placebo (-2.1 mm3; 95% CI, -4.21 to 0.07 mm3) (between-group difference, -2.04 mm3 [95% CI, -5.03 to 0.95 mm3]; P = .18). There were no significant differences in the proportion of participants who demonstrated regression of PAV (56.9% vs 48.9%; P = .08) and TAV (64.4% vs 57.5%; P = .13) in the aliskiren and placebo groups, respectively. CONCLUSIONS AND RELEVANCE: Among participants with prehypertension and coronary artery disease, the use of aliskiren compared with placebo did not result in improvement or slowing of progression of coronary atherosclerosis. These findings do not support the use of aliskiren for regression or prevention of progression of coronary atherosclerosis. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT00853827.

Inhibition of secretory phospholipase A(2) in patients with acute coronary syndromes: rationale and design of the vascular inflammation suppression to treat acute coronary syndrome for 16 weeks (VISTA-16) trial.

BACKGROUND: The action of secretory phospholipase A(2) (sPLA(2)) on lipoproteins may render them more susceptible to oxidation, thereby promoting vascular inflammation and increasing cardiovascular risk. Patients with acute coronary syndrome face a high risk of early, recurrent cardiovascular events that is associated with biomarkers of inflammation, including sPLA(2). The Vascular Inflammation Suppression to Treat Acute Coronary Syndrome for 16 Weeks (VISTA-16, NCT01130246) tests the hypothesis that varespladib methyl, an inhibitor of several sPLA(2) isoforms with a causal role in atherosclerosis, reduces cardiovascular risk among patients with acute coronary syndromes. METHODS: Up to 6,500 patients with acute coronary syndrome will be randomized to receive treatment with varespladib methyl 500 mg daily or placebo for 16 weeks, in addition to background treatment with atorvastatin and other evidence-based therapies. The primary efficacy parameter is the combination of cardiovascular death, nonfatal myocardial infarction, nonfatal stroke or hospitalization for unstable angina with objective evidence of myocardial ischemia. Effects of varespladib methyl on lipid and inflammatory markers, in addition to safety and tolerability, will also be evaluated. CONCLUSION: sPLA(2) inhibition has the potential to exert a favorable effect on the artery wall. The VISTA-16 study will determine whether varespladib methyl has a beneficial impact on cardiovascular events in patients with an acute coronary syndrome.

Assessment of omega-3 carboxylic acids in statin-treated patients with high levels of triglycerides and low levels of high-density lipoprotein cholesterol: Rationale and design of the STRENGTH trial.

It is uncertain whether omega-3 fatty acids are beneficial in statin-treated patients. Epanova is a mix of omega-3 free fatty acids, not requiring co-ingestion with food, which can lower triglycerides by up to 31%. STRENGTH will examine whether Epanova 4 g daily reduces the rate of cardiovascular events in statin-treated patients with hypertriglyceridemia and low levels of HDL-C at high risk for developing cardiovascular events. STRENGTH is a randomized, double-blind, placebo-controlled trial. Patients had a triglyceride level ≥ 180 to <500 mg/dL and HDL-C < 42 mg/dL (men) or < 47 mg/dL (women) in the presence of either (1) established atherosclerotic cardiovascular disease, (2) diabetes with one additional risk factor, or (3) were other high-risk primary prevention patients, based on age and risk factor assessment. Patients should be treated with a statin, for >4 weeks, and have LDL-C < 100 mg/dL, but were also eligible if LDL-C was ≥100 mg/dL while on maximum tolerated statin therapy. The study will extend from October 30, 2014 to October 30, 2019. 13 086 patients were randomized to Epanova 4 g or placebo daily in addition to standard medical therapy. The primary efficacy outcome is time to first event of cardiovascular death, myocardial infarction, stroke, coronary revascularization or hospitalization for unstable angina. The trial will continue until 1600 patients reach the primary endpoint, with a median duration of therapy of 3 years. STRENGTH will determine whether Epanova 4 g daily will reduce cardiovascular events in statin-treated high-risk patients with hypertriglyceridemia and low HDL-C levels.

Incidence of atrial fibrillation post-cavotricuspid isthmus ablation in patients with typical atrial flutter: left-atrial size as an independent predictor of atrial fibrillation recurrence.

INTRODUCTION: Atrial fibrillation and atrial flutter often coexist. The long-term occurrence of atrial fibrillation in patients presenting with atrial flutter alone is unknown. We report the long-term follow-up in patients who underwent cavotricuspid isthmus ablation for treatment of lone atrial flutter. METHODS AND RESULTS: Between January 1997 and June 2002, 632 patients underwent cavotricuspid isthmus ablation for the treatment of typical atrial flutter at the Cleveland Clinic Foundation. Three hundred sixty-three patients were included in this study and followed for a mean duration of 39 +/- 11 months. The mean duration of atrial flutter symptoms was 12 +/- 5 months. Mean left-atrial size and left-ventricular ejection fraction were 4.2 +/- 0.8 cm and 47 +/- 13%, respectively. After a mean follow-up time of 39 +/- 11 months, 13% (48 of 363) of the patients remained in sinus rhythm. Five percent (18 of 363) of patients experienced recurrence of atrial flutter only. Sixty-eight percent (246 of 363) experienced the onset of atrial fibrillation and 14% (51 of 363) experienced recurrence of atrial flutter and the new onset of atrial fibrillation. Overall, 82% (297 of 363) of the patients experienced new onset of drug refractory atrial fibrillation. Left-atrial size was a predictor of atrial fibrillation recurrence post-atrial flutter ablation. CONCLUSION: At long-term follow-up, approximately 82% of patients post-cavotricuspid isthmus ablation for atrial flutter developed drug refractory atrial fibrillation. This finding suggests that elimination of atrial flutter might delay, but does not prevent, atrial fibrillation. Evidence suggests both arrhythmias may share common triggers and such patients may derive a better long-term benefit from anatomical ablative treatment of atrial fibrillation as well.

Phased-array intracardiac echocardiography monitoring during pulmonary vein isolation in patients with atrial fibrillation: impact on outcome and complications.

BACKGROUND: The objective of this study was to assess the impact of intracardiac echocardiography (ICE) on the long-term success and complications in patients undergoing pulmonary vein isolation (PVI) for treatment of atrial fibrillation (AF). METHODS AND RESULTS: Three hundred fifteen patients underwent PVI for treatment of AF. Each patient underwent ostial isolation of all PVs using a cooled-tip ablation catheter. PVI was performed using circular mapping (CM) alone (group 1, 56 patients), CM and ICE (group 2, 107 patients), and CM and ICE with titration of radiofrequency energy based on visualization of microbubbles by ICE (group 3, 152 patients). After a mean follow-up time of 417+/-145 days, 19.6% (11 of 56), 16.8% (18 of 107), and 9.8% (15 of 152) of patients in groups 1, 2, and 3 experienced recurrence of AF, respectively. Moreover, whereas no group 3 patient experienced severe (>70%) PV stenosis, severe PV stenosis was documented in 3 (3.5%) of 56 patients in group 1 and in 2 (1.8%) of 107 patients in group 2 (P<0.05). No embolic events were detected in group 3 patients. CONCLUSIONS: Intracardiac echocardiography improves the outcome of cooled-tip PVI. Power adjustment guided by direct visualization of microbubble formation reduces the risk of PV stenosis and improves long-term cure.

Percutaneous pericardial instrumentation for endo-epicardial mapping of previously failed ablations.

BACKGROUND: The epicardial location of an arrhythmia could be responsible for unsuccessful endocardial catheter ablation. METHODS AND RESULTS: In 48 patients referred after prior unsuccessful endocardial ablation, we considered percutaneous, subxiphoid instrumentation of the pericardial space for mapping and ablation. Thirty patients had ventricular tachycardia (VT), 6 patients had a right- and 4 had a left-sided accessory pathway (AP), 4 patients had inappropriate sinus tachycardia, and 4 patients had atrial arrhythmias. Of the 30 VTs, 24 (6 with ischemic cardiomyopathy, 3 with idiopathic cardiomyopathy, and 15 with normal hearts) appeared to originate from the epicardium. Seventeen (71%) of these 24 VTs were successfully ablated with epicardial lesions. The other 7 VTs had early epicardial sites that were inaccessible, predominantly because of interference from the left atrial appendage. Six of these were successfully ablated from the left coronary cusp. In 5 of the 10 patients with an AP, the earliest activation was recorded epicardially. Three of these were right atrial appendage-to-right ventricle APs, and epicardial ablation was successful. No significant complications were observed. CONCLUSIONS: Failure of endocardial ablation could reflect the presence of an epicardial arrhythmia substrate. Epicardial instrumentation and ablation appeared feasible and safe and provided an alternative strategy for the treatment of patients with a variety of arrhythmias. This was particularly true for VT, including patients without structural heart disease.

Transcatheter angioplasty for acquired pulmonary vein stenosis after radiofrequency ablation.

BACKGROUND: Pulmonary vein stenosis has recently been recognized as a complication of radiofrequency ablation for atrial fibrillation. This study evaluates the presentation of affected patients and the role of transcatheter therapy for this patient population. METHODS AND RESULTS: This study used a retrospective review of data from 19 patients (age, 51+/-13 years) with pulmonary vein stenosis who underwent catheterization and angiography between December 2000 and December 2002. Quantitative perfusion and spiral CT scans were performed for initial diagnosis and follow-up. The median duration between radiofrequency ablation and the reported onset of respiratory symptoms for 18 of 19 patients was 7.5 weeks (0.1 to 48). After the onset of symptoms, all but two patients were initially misdiagnosed with a symptoms-to-diagnosis duration of 16 weeks (2-59). At initial catheterization, 17 of 19 patients had angioplasty in 30 veins with stent placement in 5 vessels when a flap occurred. Overall vessel diameter increased from 2.6+/-1.6 to 6.6+/-2.4 mm (P<0.0001). There were 4 procedure-related adverse events but no long-term sequelae. Immediate follow-up showed improved flow to involved lung segments. At a median follow-up of 43 weeks (2-92), although repeat angioplasty for restenosis was necessary in 8 of 17 patients, 15 of 17 patients currently have no or minimal persistent symptoms. CONCLUSIONS: Pulmonary vein stenosis after radiofrequency ablation for atrial fibrillation is often misdiagnosed. Although further follow-up is necessary to determine long-term success, our data indicate better pulmonary vein flow and symptomatic improvement in the majority of patients undergoing dilation of postablation pulmonary vein stenosis.

Randomized study comparing combined pulmonary vein-left atrial junction disconnection and cavotricuspid isthmus ablation versus pulmonary vein-left atrial junction disconnection alone in patients presenting with typical atrial flutter and atrial fibrillation.

BACKGROUND: Atrial flutter (AFL) and atrial fibrillation (AF) frequently coexist in the same patient. Recently it has been demonstrated that the triggers for both AF and AFL may originate in the pulmonary veins (PVs). We hypothesized that in patients with both AF and typical AFL, pulmonary vein-left atrial junction (PV-LAJ) disconnection may eliminate both arrhythmias. METHODS AND RESULTS: Consecutive patients with documented symptomatic AF and typical AFL were randomly assigned to have PV-LAJ disconnection combined with cavotricuspid isthmus (CTI) ablation (group 1, n=49) or PV-LAJ disconnection alone (group 2, n=59). Within the first 8 weeks after ablation, 32 of the group 2 patients had typical AFL documented, whereas none was seen in group 1. Twenty of these 32 converted to sinus rhythm after initiating antiarrhythmic drugs (AADs). Twelve were cardioverted, and AADs were started. After 8 weeks, all AADS were stopped, and only 3 patients continued to have recurrent sustained typical AFL that was eliminated by CTI ablation. Beyond 8 weeks of follow-up, 7 patients in group 1 and 6 patients in group 2 (14% and 11%, respectively) continued to have AF. Ten of these 13 patients underwent a repeat PV-LAJ disconnection procedure and were cured. The remaining 3 remained in normal sinus rhythm while taking AADs. CONCLUSIONS: In patients with both AFL and AF, PV-LAJ disconnection alone may be sufficient to control both arrhythmias. CTI block reduced early postablation recurrence of arrhythmias, which in the majority of patients reflects a short-term clinical problem.

Pulmonary vein stenosis after radiofrequency ablation of atrial fibrillation: functional characterization, evolution, and influence of the ablation strategy.

BACKGROUND: Pulmonary vein (PV) stenosis is a complication of ablation for atrial fibrillation. The impact of different ablation strategies on the incidence of PV stenosis and its functional characterization has not been described. METHODS AND RESULTS: PV isolation was performed in 608 patients. An electroanatomic approach was used in 71 and circular mapping in 537 (distal isolation, 25; ostial isolation based on PV angiography, 102; guided by intracardiac echocardiography, 140; with energy delivery based on visualization of microbubbles, 270). Severe (> or =70%) narrowing was detected in 21 patients (3.4%), and moderate (50% to 69%) and mild (<50%) narrowing occurred in 27 (4.4%) and 47 (7.7%), respectively. Severe stenosis occurred in 15.5%, 20%, 2.9%, 1.4%, and 0%, respectively. Development of symptoms was correlated with involvement of >1 PV with severe narrowing (P=0.01), whereas all patients with mild and moderate narrowing were asymptomatic. In the latter group, lung perfusion (V/Q) scans were normal in all but 4 patients. All patients with severe stenosis had abnormal perfusion scans. CONCLUSIONS: V/Q scans are useful to assess the functional significance of PV stenosis. Mild and moderate degrees of PV narrowing are not associated with development of symptoms and seem to have no or minimal detrimental effect on pulmonary flow. The incidence of severe PV stenosis seems to be declining with better imaging techniques to ensure ostial isolation and to guide power titration. Mild narrowing 3 months after ablation does not preclude future development of severe stenosis and should be assessed with repeat imaging studies.

Three-dimensional nonfluoroscopic mapping and ablation of inappropriate sinus tachycardia. Procedural strategies and long-term outcome.

OBJECTIVES: We conducted this study to assess long-term results of three-dimensional (3-D) mapping-guided radiofrequency ablation (RFA) of inappropriate sinus tachycardia (IST). Change in activation after the administration of esmolol was also assessed and compared to the shift documented with successful sinus node (SN) modification. BACKGROUND: The long-term results after RFA of IST have been reported to vary between 27% and 66%. METHODS: Thirty-nine patients (35 women, mean age 31 +/- 9 years) with debilitating IST were included in the study. The area around the earliest site of activation recorded using the 3-D mapping system was targeted for ablation. The shift in the earliest activation site after administration of esmolol was compared with the shift after RFA. RESULTS: The heart rate at rest and in drug-free state ranged between 95 and 125 beats/min (mean 99 +/- 14 beats/min). Sinus node was successfully modified in all patients. Following ablation, the mean heart rate dropped to 72 +/- 8 beats/min, p < 0.01. The extent of the 3-D shift in caudal activation along the crista terminalis was more pronounced after RFA than during esmolol administration (23 +/- 11 mm vs. 7 +/- 5 mm, respectively, p < 0.05). No patient required pacemaker implantation after a mean follow-up time of 32 +/- 9 months; 21% of patients experienced recurrence of IST and were successfully re-ablated. CONCLUSIONS: Three-dimensional electroanatomical mapping seems to facilitate and improve the ablation results of IST. The difference in caudal shift seen after esmolol administration and following SN modification suggests that adrenergic hypersensitivity is not the only mechanism responsible for the inappropriate behavior of the SN.

Circular mapping and ablation of the pulmonary vein for treatment of atrial fibrillation: impact of different catheter technologies.

OBJECTIVES: We conducted this study to compare the efficacy and safety of different catheter ablation technologies and of distal versus ostial pulmonary veins (PV) isolation using the circular mapping technique. BACKGROUND: Electrical isolation of the PVs in patients with atrial fibrillation (AF) remains a technical challenge. METHODS: Two hundred eleven patients (163 men; mean age 53 +/- 11 years) with symptomatic AF were included in this study. In the first 21 patients (group 1), distal isolation (> or = 5 mm from the ostium) was achieved targeting veins triggering AF. In the remaining 190 patients (group 2), ostial isolation of all PVs was performed using 4-mm tip (47 patients), 8-mm tip (21 patients), or cooled-tip (122 patients) ablation catheters. RESULTS: Distal isolation was able to eliminate premature atrial contractions (PACs) and AF in six of 21 patients (29%) and 10 of 34 PVs. After a mean follow-up time of 6 +/- 4 months, no patients treated with the 8-mm tip catheter experienced recurrence of AF, whereas 21% (10 of 47 patients) and 15% (18 of 122 patients) of the patients ablated with the 4-mm tip and the cooled-tip ablation catheters experienced recurrence of AF after a mean follow-up of 10 +/- 3 and 4 +/- 2 months, respectively. Significant complications including stroke, tamponade, and severe stenosis occurred in 3.5% (8/211) of patients. CONCLUSIONS: Catheter technologies designed to achieve better lesion size appeared to have a positive impact on procedure time, fluoroscopy time, number of lesions, and overall efficacy. Although distal isolation can be achieved with fewer lesions, ostial isolation is required in the majority of patients to eliminate arrhythmogenic PACs and AF.

Mode of initiation and ablation of ventricular fibrillation storms in patients with ischemic cardiomyopathy.

OBJECTIVES: We report on the initiation of ventricular fibrillation (VF) storm in patients with ischemic cardiomyopathy (ICM) and the results of targeted ablation to treat VF storm. BACKGROUND: Monomorphic premature ventricular contractions (PVCs) have been shown to initiate VF in patients without structural heart disease. METHODS: A total of 29 patients with ICM and documented VF initiation were identified. In 21 patients, VF storm was controlled with antiarrhythmic drugs and/or treatment of heart failure. Eight patients with VF (mean 52 +/- 25 episodes) refractory to medical management required ablation. All patients underwent three-dimensional electroanatomical mapping using CARTO (Biosense-Webster Inc., Diamond Bar, California), and PVCs were mapped when present. Scarred areas were identified using voltage mapping. RESULTS: Monomorphic PVCs initiated VF in all 29 identified patients. Five of eight patients requiring ablation had frequent PVCs that allowed PVC mapping. The earliest activation site was consistently located in the scar border zone. The PVCs were always preceded by a Purkinje-like potential (PLP). Ablation was successfully performed at these sites. In three patients, infrequent PVCs prevented mapping, but PLPs were recorded around the scar border. Ablation targeting these potentials along the scar border was successfully performed. During follow-up (10 +/- 6 months), one patient had a single VF episode and another developed sustained, monomorphic ventricular tachycardia. There was no recurrence of VF storm. CONCLUSIONS: Ventricular fibrillation in ICM is triggered by monomorphic PVCs originating from the scar border zone with preceding PLPs; targeting these PVCs may prevent VF recurrence. In the absence of PVCs, both substrate mapping and ablation appear to be equally effective.

Pulmonary vein isolation for the treatment of atrial fibrillation in patients with impaired systolic function.

OBJECTIVES: We aimed to determine the safety and efficacy of pulmonary vein isolation (PVI) in atrial fibrillation (AF) patients with impaired left ventricular (LV) systolic function. BACKGROUND: To date, PVI has been performed primarily in patients with normal LV function. Yet, many AF patients have impaired LV systolic function. The outcomes of PVI in patients with impaired LV systolic function are unknown. METHODS: We included 377 consecutive patients undergoing PVI between December 2000 and January 2003. Ninety-four patients had impaired LV function (ejection fraction [EF] <40%), and they comprised the study group. The control group was the remaining 283 patients who had a normal EF. End points included AF recurrence and changes in EF and quality of life (QoL). RESULTS: Mean EF was 36% in our study group, compared with 54% in controls. After initial PVI, 73% of patients with impaired EF and 87% of patients with normal EF were free of AF recurrence at 14 +/- 6 months (p = 0.03). In the study group, there was a nonsignificant increase in EF of 4.6% and significant improvement in QoL. Complication rates were low and included a 1% risk of pulmonary vein stenosis. CONCLUSIONS: Although the AF recurrence rate after initial PVI in impaired EF patients was higher than in normal EF subjects, nearly three-fourths of patients with impaired EF remained AF-free. Although our sample size was nonrandomized, our results suggest PVI may be a feasible therapeutic option in AF patients with impaired EF. Randomized studies with more patients and longer follow-up are warranted.

Pulmonary vein stenosis after catheter ablation of atrial fibrillation: emergence of a new clinical syndrome.

BACKGROUND: Pulmonary vein isolation is a new, effective curative procedure for selected patients with atrial fibrillation. Pulmonary vein stenosis is a potential complication and may lead to symptoms that are often underrecognized. OBJECTIVE: To describe the clinical course and symptoms associated with pulmonary vein stenosis developing after ablation in the pulmonary veins. DESIGN: Retrospective study. SETTING: Tertiary care referral center. PATIENTS: 335 patients referred for catheter ablation of drug-refractory atrial fibrillation. INTERVENTION: Pulmonary vein electrical isolation using radiofrequency catheter ablation. MEASUREMENTS: Three months after ablation, patients underwent routine screening for pulmonary vein stenosis with spiral computed tomography. Screening was considered earlier if symptoms suggestive of stenosis developed and was repeated at 6 and 12 months if any pulmonary vein narrowing was observed. Pulmonary vein angiography and dilatation were offered to patients with severe (>70%) stenosis. RESULTS: Severe pulmonary vein stenosis was detected in 18 patients (5% [95% CI, 3.2% to 8.4%]) a mean (+/-SD) of 5.2 +/- 2.6 months after ablation. Eight of these 18 patients (44%) were asymptomatic, but 8 (44%) reported shortness of breath, 7 (39%) reported cough, and 5 (28%) reported hemoptysis. Radiologic abnormalities were present in 9 patients (50%) and led to diagnoses of pneumonia (4 patients), lung cancer (1 patient), and pulmonary embolism (2 patients). Pulmonary vein stenosis was not considered in any patient during the initial work-up. Dilatation of the affected vein was performed in 12 patients. Postintervention lung perfusion scans revealed significant improvement in lung flow. CONCLUSIONS: Severe pulmonary vein stenosis after catheter ablation of atrial fibrillation is associated with respiratory symptoms that frequently mimic more common diseases, often leading to erroneous diagnostic and therapeutic procedures. Awareness of this syndrome is important for proper and prompt management.

Radiofrequency ablation vs antiarrhythmic drugs as first-line treatment of symptomatic atrial fibrillation: a randomized trial.

CONTEXT: Treatment with antiarrhythmic drugs and anticoagulation is considered first-line therapy in patients with symptomatic atrial fibrillation (AF). Pulmonary vein isolation (PVI) with radiofrequency ablation may cure AF, obviating the need for antiarrhythmic drugs and anticoagulation. OBJECTIVE: To determine whether PVI is feasible as first-line therapy for treating patients with symptomatic AF. DESIGN, SETTING, AND PARTICIPANTS: A multicenter prospective randomized study conducted from December 31, 2001, to July 1, 2002, of 70 patients aged 18 to 75 years who experienced monthly symptomatic AF episodes for at least 3 months and had not been treated with antiarrhythmic drugs. INTERVENTION: Patients were randomized to receive either PVI using radiofrequency ablation (n=33) or antiarrhythmic drug treatment (n=37), with a 1-year follow-up. MAIN OUTCOME MEASURES: Recurrence of AF, hospitalization, and quality of life assessment. RESULTS: Two patients in the antiarrhythmic drug treatment group and 1 patient in the PVI group were lost to follow-up. At the end of 1-year follow-up, 22 (63%) of 35 patients who received antiarrhythmic drugs had at least 1 recurrence of symptomatic AF compared with 4 (13%) of 32 patients who received PVI (P<.001). Hospitalization during 1-year follow-up occurred in 19 (54%) of 35 patients in the antiarrhythmic drug group compared with 3 (9%) of 32 in the PVI group (P<.001). In the antiarrhythmic drug group, the mean (SD) number of AF episodes decreased from 12 (7) to 6 (4), after initiating therapy (P = .01). At 6-month follow-up, the improvement in quality of life of patients in the PVI group was significantly better than the improvement in the antiarrhythmic drug group in 5 subclasses of the Short-Form 36 health survey. There were no thromboembolic events in either group. Asymptomatic mild or moderate pulmonary vein stenosis was documented in 2 (6%) of 32 patients in the PVI group. CONCLUSION: Pulmonary vein isolation appears to be a feasible first-line approach for treating patients with symptomatic AF. Larger studies are needed to confirm its safety and efficacy.

Pulmonary vein antrum isolation for treatment of atrial fibrillation in patients with valvular heart disease or prior open heart surgery.

OBJECTIVES: The goal of this study was to assess the safety and efficacy of pulmonary vein antrum isolation in patients with moderate valvular heart disease or open-heart surgery and atrial fibrillation (AF). BACKGROUND: Valvular heart disease and open-heart surgery are commonly associated with AF and increase the risk of adverse events in AF patients. METHODS: A total of 391 consecutive patients who had pulmonary vein antrum isolation performed between December 2000 and December 2002 were screened. A total of 142 of these patients had clinically significant valvular disease or prior cardiac surgery. End points included AF recurrence and pulmonary vein antrum isolation complication rates. RESULTS: Patients with valvular heart disease or prior open-heart surgery were older, had larger left atria and a more advanced New York Heart Association class. They did not differ significantly with respect to gender, but had a longer history of AF. Procedure times were similar between patients with and without valvular heart disease or prior open-heart surgery. After 18 +/- 7 months in the lone AF patients, 11 +/- 5 months in patients with valvular heart disease, and 10 +/- 5 months in patients with prior open heart surgery, there was a trend toward lower recurrence of AF in patients with lone AF who enjoyed a 98% overall cure rate after up to 2 pulmonary vein antrum isolations versus 93% among patients with valvular heart disease (P = .04) and prior open heart surgery (P = .07). Complication rates were comparable between groups. CONCLUSIONS: Pulmonary vein antrum isolation is safe and effective in patients with moderate valvular heart disease and the patients who developed AF after open-heart surgery. These results have implications for our understanding of the pathophysiology of AF in patients with moderate valvular heart disease or past cardiac surgery and should be considered when discussing treatment options in these patients.

Embolic events and char formation during pulmonary vein isolation in patients with atrial fibrillation: impact of different anticoagulation regimens and importance of intracardiac echo imaging.

UNLABELLED: Thromboembolic events are important complications of pulmonary vein isolation (PVI) procedures, occurring in up to 2.8% of patients. In this study, we report the incidence of char formation and embolic events with different anticoagulation protocols prospectively changed to reduce such complication. METHODS: A total of 785 patients (mean age: 54 years, 83.5% male) underwent catheter-based PVI for treatment of drug refractory, symptomatic atrial fibrillation (AF). PVI was performed utilizing different strategies including radiofrequency (RF) using temperature control energy delivery and RF using intracardiac echocardiography (ICE)-guided power titration. Patients were divided based on the anticoagulation protocol into three groups: in group 1 (194 patients), activation coagulation time (ACT) was maintained between 250 and 300 seconds; in group 2 (180 patients), ACT was maintained between 300 and 350 seconds plus the IV infusion of eptifibatide (135 microg/kg bolus + 0.5 microg/kg/min); and in group 3 (411 patients), ACT was maintained between 350 and 400 seconds. RESULTS: Char formation was detected in 69 patients of group 1, 5 of group 2, and 8 of group 3. An embolic event was observed in 7 patients of group 1, 3 of group 2, and 2 of group 3 (P = 0.01; group 1 vs group 3). Higher degree of anticoagulation with heparin was associated with a reduced incidence of embolic events even after removing the patients undergoing ICE-guided ablation (P = 0.04). CONCLUSION: More aggressive anticoagulation with heparin reduced periprocedural embolic events. The use of platelet inhibition does not have incremental beneficial effect. None of the anticoagulation protocol abolished char formation.

Use of different catheter ablation technologies for treatment of typical atrial flutter: acute results and long-term follow-up.

OBJECTIVES: We report the acute success and long-term follow-up in consecutive patients undergoing catheter ablation of typical right atrial flutter (AFL) using different ablation technologies. METHODS: One hundred and two patients presenting for treatment of AFL to our laboratory were included in the study. Based on availability and physician preference, ablation was performed with either a cooled-tip catheter (39 patients, group I), an 8- or 10-mm tip catheter connected to a high-power radiofrequency (RF) generator (25 patients, group II), or a 4- or 5-mm tip catheter (38 patients, group III). Acute ablation success was achieved in all group II and group III patients. Among the 38 patients undergoing ablation with the conventional catheter tip (group I), crossover to an 8-mm tip or a cooled tip ablation catheter was required in 11 patients (29%). The mean fluoroscopy time was significantly higher in group I (54.3 +/- 26.4 minutes) when compared to group II (39.6 +/- 19.6 minutes; P < 0.05) and group III (40 +/- 16 minutes; P = 0.0.5). After a mean follow up of 20 +/- 5 months no patient in group II experienced recurrence of AFL, whereas 18.4% (7 of 38 patients; P < 0.05) in group I and 10% (4 of 39 patients; P < 0.05) in group III had recurrence of AFL. Ablation technologies designed to obtain larger size lesions appeared to be more effective in achieving acute ablation success of AFL and in limiting the long-term recurrence rate of this arrhythmia.