Safety, Performance, and Efficacy of Cardiac Contractility Modulation Delivered by the 2-Lead Optimizer Smart System: The FIX-HF-5C2 Study.

BACKGROUND: Prior studies of cardiac contractility modulation (CCM) employed a 3-lead Optimizer system. A new 2-lead system eliminated the need for an atrial lead. This study tested the safety and effectiveness of this 2-lead system compared with the 3-lead system. METHODS: Patients with New York Heart Association III/IVa symptoms despite medical therapy, left ventricular ejection fraction 25% to 45%, and not eligible for cardiac resynchronization therapy could participate. All subjects received an Optimizer 2-lead implant. The primary end point was the estimated difference in the change of peak VO2 from baseline to 24 weeks between FIX-HF-5C2 (2-lead system) subjects relative to control subjects from the prior FIX-HF-5C (3-lead system) study. Changes in New York Heart Association were a secondary end point. The primary safety end point was a comparison of device-related adverse events between FIX-HF-5C2 and FIX-HF-5C subjects. RESULTS: Sixty subjects, 88% male, 66±9 years old with left ventricular ejection fraction 34±6% were included. Baseline characteristics were similar between FIX-HF-5C and FIX-HF-5C2 subjects except that 15% of FIX-HF-5C2 subjects had permanent atrial fibrillation versus 0% in FIX-HF-5C. CCM delivery did not differ significantly between 2- and 3-lead systems (19 892±3472 versus 19 583±4998 CCM signals/day, CI of difference [-1228 to 1847]). The change of peak VO2 from baseline to 24 weeks was 1.72 (95% Bayesian credible interval, 1.02-2.42) mL/kg per minute greater in the 2-lead device group versus controls. 83.1% of 2-lead subjects compared with 42.7% of controls experienced ≥1 class New York Heart Association improvement (P<0.001). There were decreased Optimizer-related adverse events with the 2-lead system compared with the 3-lead system (0% versus 8%; P=0.03). CONCLUSIONS: The 2-lead system effectively delivers comparable amount of CCM signals (including in subjects with atrial fibrillation) as the 3-lead system, is equally safe and improves peak VO2 and New York Heart Association. Device-related adverse effects are less with the 2-lead system. Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03339310.

A Randomized Controlled Trial to Evaluate the Safety and Efficacy of Cardiac Contractility Modulation.

OBJECTIVES: This study sought to confirm a subgroup analysis of the prior FIX-HF-5 (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure) study showing that cardiac contractility modulation (CCM) improved exercise tolerance (ET) and quality of life in patients with ejection fractions between 25% and 45%. BACKGROUND: CCM therapy for New York Heart Association (NYHA) functional class III and IV heart failure (HF) patients consists of nonexcitatory electrical signals delivered to the heart during the absolute refractory period. METHODS: A total of 160 patients with NYHA functional class III or IV symptoms, QRS duration <130 ms, and ejection fraction ≥25% and ≤45% were randomized to continued medical therapy (control, n = 86) or CCM (treatment, n = 74, unblinded) for 24 weeks. Peak Vo2 (primary endpoint), Minnesota Living With Heart Failure questionnaire, NYHA functional class, and 6-min hall walk were measured at baseline and at 12 and 24 weeks. Bayesian repeated measures linear modeling was used for the primary endpoint analysis with 30% borrowing from the FIX-HF-5 subgroup. Safety was assessed by the percentage of patients free of device-related adverse events with a pre-specified lower bound of 70%. RESULTS: The difference in peak Vo2 between groups was 0.84 (95% Bayesian credible interval: 0.123 to 1.552) ml O2/kg/min, satisfying the primary endpoint. Minnesota Living With Heart Failure questionnaire (p < 0.001), NYHA functional class (p < 0.001), and 6-min hall walk (p = 0.02) were all better in the treatment versus control group. There were 7 device-related events, yielding a lower bound of 80% of patients free of events, satisfying the primary safety endpoint. The composite of cardiovascular death and HF hospitalizations was reduced from 10.8% to 2.9% (p = 0.048). CONCLUSIONS: CCM is safe, improves exercise tolerance and quality of life in the specified group of HF patients, and leads to fewer HF hospitalizations. (Evaluate Safety and Efficacy of the OPTIMIZER System in Subjects With Moderate-to-Severe Heart Failure; NCT01381172).

The effect of ablation electrode length and catheter tip to endocardial orientation on radiofrequency lesion size in the canine right atrium.

Although the determinants of radiofrequency lesion size have been characterized in vitro and in ventricular tissue in situ, the effects of catheter tip length and endocardial surface orientation on lesion generation in atrial tissue have not been studied. Therefore, the dimensions of radiofrequency lesions produced with 4-, 6-, 8-, 10-, and 12-mm distal electrode lengths were characterized in 26 closed-chested dogs. The impact of parallel versus perpendicular catheter tip/endocardial surface orientation, established by biplane fluoroscopy and/or intracardiac echocardiography, on lesion dimensions was also assessed. Radiofrequency voltage was titrated to maintain a steady catheter tip temperature of 75 degrees C for 60 seconds. With a perpendicular catheter tip/tissue orientation, the lesion area increased from 29 +/- 7 mm2 with a 4-mm tip to 42 +/- 12 mm2 with the 10-mm tip, but decreased to 29 +/- 8 mm2 with ablation via a 12-mm tip. With a parallel distal tip/endocardial surface orientation, lesion areas were significantly greater: 54 +/- 22 mm2 with a 4-mm tip, 96 +/- 28 mm2 with a 10-mm tip and 68 +/- 24 mm2 with a 12-mm tip (all P < 0.001 vs perpendicular orientation). Lesion lengths and apparent volumes were larger with parallel, compared to perpendicular tip/tissue orientations, although lesion depth was independent of catheter tip length with both catheter tip/tissue orientations. Electrode edge effects were not observed with any tip length. Direct visualization using intracardiac ultrasound guidance was subjectively helpful in insuring an appropriate catheter tip/tissue interface needed to maximize lesion size. Although atrial lesion size is critically dependent on catheter tip length, it is more influenced by the catheter orientation to the endocardial surface. This information may also be helpful in designing electrode arrays for the creation of continuous linear lesions for the elimination of complex atrial tachyarrhythmias.