Stuart W. Adler

BACKGROUND: The effects of cardiac resynchronization therapy (CRT) in patients with mildly symptomatic heart failure have not been fully elucidated. METHODS AND RESULTS: The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction < or =35%, a QRS > or =130 ms, and a class I indication for an ICD. One hundred eighty-six patients were randomized: 101 to the control group (ICD activated, CRT off) and 85 to the CRT group (ICD activated, CRT on). End points included peak VO2, VE/CO2, NYHA class, quality of life, 6-minute walk distance, LV volumes and ejection fraction, and composite clinical response. Compared with the control group at 6 months, no significant improvement was noted in peak VO2, yet there were significant improvements in ventricular remodeling indexes, specifically LV diastolic and systolic volumes (P=0.04 and P=0.01, respectively), and LV ejection fraction (P=0.02). CRT patients showed statistically significant improvement in VE/CO2 (P=0.01), NYHA class (P=0.05), and clinical composite response (P=0.01). No significant differences were noted in 6-minute walk distance or quality of life scores. CONCLUSIONS: In patients with mild heart failure symptoms on optimal medical therapy with a wide QRS complex and an ICD indication, CRT did not alter exercise capacity but did result in significant improvement in cardiac structure and function and composite clinical response over 6 months.

Background: Left atrial appendage (LAA) occlusion provides an alternative to oral anticoagulation for thromboembolic risk reduction in patients with nonvalvular atrial fibrillation. Since regulatory approval in 2015, the WATCHMAN device has been the only LAA closure device available for clinical use in the United States. The PINNACLE FLX study (Protection Against Embolism for Nonvalvular AF Patients: Investigational Device Evaluation of the Watchman FLX LAA Closure Technology) evaluated the safety and effectiveness of the next-generation WATCHMAN FLX LAA closure device in patients with nonvalvular atrial fibrillation in whom oral anticoagulation is indicated, but who have an appropriate rationale to seek a nonpharmaceutical alternative. Methods: This was a prospective, nonrandomized, multicenter US Food and Drug Administration study. The primary safety end point was the occurrence of one of the following events within 7 days after the procedure or by hospital discharge, whichever was later: death, ischemic stroke, systemic embolism, or device- or procedure-related events requiring cardiac surgery. The primary effectiveness end point was the incidence of effective LAA closure (peri-device flow ≤5 mm), as assessed by the echocardiography core laboratory at 12-month follow-up. Results: A total of 400 patients were enrolled. The mean age was 73.8±8.6 years and the mean CHA 2 DS 2 -VASc score was 4.2±1.5. The incidence of the primary safety end point was 0.5% with a 1-sided 95% upper CI of 1.6%, meeting the performance goal of 4.2% ( P &lt;0.0001). The incidence of the primary effectiveness end point was 100%, with a 1-sided 95% lower CI of 99.1%, again meeting the performance goal of 97.0% ( P &lt;0.0001). Device-related thrombus was reported in 7 patients, no patients experienced pericardial effusion requiring open cardiac surgery, and there were no device embolizations. Conclusions: LAA closure with this next-generation LAA closure device was associated with a low incidence of adverse events and a high incidence of anatomic closure. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02702271.

INTRODUCTION: Atrial pacing locations that decrease atrial activation and recovery time may be preferable in patients with a history of atrial arrhythmias. This multicenter prospective randomized study compared the efficacy of Bachmann's bundle (BB) region pacing to right atrial appendage (RAA) pacing in patients with recurrent paroxysmal atrial fibrillation (AF). METHODS AND RESULTS: Patients with standard pacing indications (n = 120, 70+/-11 years) were randomized to atrial pacing in either the RAA (n = 57) or BB region (n = 63). Implantation time was similar between groups (88+/-36 min [n = 38] for BB vs 83+/-34 min [n = 34] for RAA). No differences in pacing threshold, impedance, or sensing between BB and RAA groups were observed at implantation or after the 6-week, 6-month, and 1-year follow-up periods. Average length of follow-up was 12.6+/-7.4 months for the BB group and 11.8+/-8.0 months for the RAA pacing group. The percentage of atrial pacing was similar between groups (61%+/-34% RAA vs 65%+/-31% BB at 2 weeks after implant). BB atrial pacing significantly (P < 0.05) shortened p wave duration compared with sinus rhythm (123+/-21 msec vs 132+/-21 msec, n = 50) 2 weeks after implant. In contrast, p wave duration was longer during atrial pacing from the RAA position compared with sinus rhythm (148+/-23 msec vs 123+/-23 msec, n = 37). Additionally, p wave duration was shorter during BB pacing than during RAA pacing. Patients with BB pacing had a higher (P < 0.05) rate of survival free from chronic AF (75%) compared with patients with RAA pacing (47%) at 1 year. CONCLUSION: BB region pacing is safe and effective for attenuating the progression of AF.

INTRODUCTION: The combined role of atrial septal lead location and atrial pacing algorithms in the prevention of atrial tachyarrhythmias (AT/AF), including both atrial fibrillation and flutter, is unknown. We tested the hypothesis that atrial prevention pacing algorithms could decrease AT/AF frequency in patients with atrial septal leads, bradycardia, and paroxysmal AT/AF. METHODS AND RESULTS: A total of 298 patients (age 70 +/- 10 years; 61% male) from 35 centers were implanted with a DDDRP pacing system including three AT/AF prevention pacing algorithms. Lead site was randomized at implant to right atrial septal or nonseptal. Patients were randomized 1 month postimplant to AT/AF prevention ON or OFF for 3 months and then crossed over for 3 months. Patients logged symptomatic AT/AF episodes via a manual activator. Prevention efficacy was evaluated based on intention-to-treat in 277 patients (138 septal) with complete follow-up. No changes in device-recorded AT/AF frequency or burden were observed with algorithms OFF versus ON or between patients randomized to septal versus nonseptal lead location. Analysis of other secondary outcomes revealed that AT/AF prevention pacing resulted in decreased atrial premature contractions in both the septal (1.9 [0.2-8.7] vs 3.3 [0.3-10.6]x 103/day; P < 0.01) and nonseptal groups (0.9 [0.2-3.3] vs 1.3 [0.3-5.5]x 103/day; P < 0.001). Patients with septal leads had fewer symptomatic AT/AF episodes ON versus OFF (1.4 +/- 3.0 vs 2.5 +/- 5.2/month, P = 0.01). CONCLUSION: The combination of three atrial prevention pacing algorithms did not decrease device classified atrial tachyarrhythmia frequency or burden during a 3-month cross-over period in bradycardic patients and septal or nonseptal atrial pacing leads. Prevention pacing was associated with decreased frequency of premature atrial contractions and with decreased symptomatic atrial tachyarrhythmia frequency in patients with atrial septal leads.