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).

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 VO 2 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 VO 2 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 VO 2 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

While some factors influencing size of RF lesions in ventricular tissue have been characterized, the effects of catheter electrode-endocardial surface orientation on lesion generation have not been investigated. Therefore, the effects of parallel versus perpendicular catheter electrode-endocardial surface orientation on dimensions of RF lesion produced with 4-, 6-, 8-, 10-, and 12-mm distal electrode lengths were studied in 20 closed-chested dogs. Orientation was established by biplane fluoroscopy and confirmed by intracardiac echocardiography for the majority of energy deliveries (71%). RF voltage was titrated to maintain constant catheter electrode temperature of 75 degrees C for 60 seconds. In the perpendicular orientation, lesion size did not change significantly with increasing electrode lengths. There was a statistically significant interaction between electrode orientation and maximum lesion length (analysis of variance [ANOVA] P = 0.04], lesion width (ANOVA P = 0.01), lesion area (ANOVA P = 0.02), and estimated lesion volume (ANOVA P < 0.005) over all electrode lengths. With parallel tip-tissue orientation, lesion size was a function of increasing electrode length. For 4-, 6-, 8-, 10-, and 12-mm electrodes, maximum lesion surface areas were 95 +/- 38, 97 +/- 38, 119 +/- 29, 147 +/- 52, and 147 +/- 67 mm2, respectively. For electrode lengths 8, 10, and 12 mm, estimated lesion volumes were significantly greater with parallel orientation (P < 0.05 for all). Thus, ventricular lesion size is dependent on catheter electrode length, but only when the catheter is oriented parallel to the endocardial surface. This information may be helpful in increasing lesion dimensions for RF ablation of ventricular tachycardias.

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.

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