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.

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.

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.

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.

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.

Circumferential ultrasound ablation for pulmonary vein isolation: analysis of acute and chronic failures.

INTRODUCTION: In patients undergoing circumferential isolation of the pulmonary veins with an ultrasound ablation system, we analyzed the temperatures achieved while delivering circumferential ostial lesions in the pulmonary veins. We also reviewed the angiograms obtained during the procedure and identified anatomic variants that could be responsible for ineffective lesion formation. METHODS AND RESULTS: During the early clinical use in 33 patients, a total of 85 veins were ablated. A mean of 16.9 +/- 12.3 ablations were delivered per patient, and a mean of 6.7 ablations per vein were applied. Entry block was assessed by placing a deflectable octapolar or a circular catheter in the vein. The following anatomic characteristics and technical limitations were identified as possible reasons for ineffective energy delivery: (1) funnel-shaped ostium; (2) ostial diameter larger than the balloon diameter; (3) inability to deliver the catheter to the right inferior or other vein ostia; (4) ostial instability; (5) early branching of the vein; and (6) eccentric position of the ultrasound transducer in the vein. In patients with recurrence of atrial fibrillation, 40% of the ostial lesions reached a temperature >60 degrees C. However, in patients cured by the ablation, 64% of the ostial lesions reached a temperature >60 degrees C (P < 0.06). At least 12 of the 20 chronic recurrences could have been related to technical limitations of the first system. Duration of atrial fibrillation and eccentric deployment of the ultrasound transducer were more frequent in patients with recurrence of arrhythmias at follow-up. CONCLUSION: Ostial anatomy of the veins may affect delivery of ultrasound energy to achieve circumferential lesions. Energy delivery at the ostium with a temperature > 60 degrees C may be important to maximize success. Reconfiguration of the system to overcome the shortcomings identified in the initial experience could increase its performance.

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.

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.