Synchronized Diaphragmatic Stimulation for Heart Failure With a Reduced Left Ventricular Ejection Fraction Using the VisONE System: A First-in-Patient Study With Extended Population

BACKGROUND: Synchronized diaphragmatic stimulation (SDS) produces localized contractions of the diaphragm gated to the cardiac cycle to transiently modulate intrathoracic pressures, thereby impacting cardiac function for heart failure patients with reduced ejection fraction (HFrEF). This study prospectively evaluated the safety and 1-year effectiveness of SDS in an expanded first-in-patient cohort using multiple implant methods. METHODS: Symptomatic patients with HFrEF despite guideline-directed therapy were enrolled. Patients were evaluated at 3, 6 and 12 months for adverse events, quality of life (SF-36 QOL), echocardiography and 6-minute hall walk distance. The SDS system consists of 2 bipolar, active-fixation leads, and an implantable pulse generator. RESULTS: Nineteen men were enrolled (age 63 [57, 67] years, New York Heart Association class II [53%]/III [47%], N-terminal pro B-type natriuretic peptide 1779 [886, 2309] pg/mL, left ventricular ejection fraction 27 [23, 33] %). Three implant techniques (abdominal laparoscopy: sensing and stimulating leads on the inferior diaphragm (n = 15); subxiphoid access for an epicardial sensing lead and abdominal laparoscopy for stimulation on the inferior diaphragm (n = 2); thoracoscopy to place an epicardial sensing lead and a stimulating lead on the superior diaphragm (n = 2)) were employed with 100% success. Patients were unaware of diaphragmatic stimulation. From discharge to 12 months, 6-minute hall walk distance increased (315 [296, 332]m to 340 [319, 384]m; p = 0.002), left ventricular end-systolic volume decreased (135 [114, 140]mL to 99 [90, 105]mL; p = 0.04), and SF-36 QOL improved (physical scale 0 [0, 0] to 25 [0, 50], p = 0.004; emotional scale 0 [0, 33] to 67 [33, 67], p = 0.001). N-terminal pro B-type natriuretic peptide was lower (1784 [944, 2659]pg/mL vs. 962 [671, 1960]pg/mL; p = ns) and left ventricular ejection fraction increased (28 [23, 38]% vs. 35 [31, 40]%; p = ns) although neither reached statistical significance. There were no procedure- or SDS-related adverse events. CONCLUSIONS: These data demonstrate that SDS can be delivered using alternative implantation methods without raising safety concerns and suggest improved outcomes over 1 ​year of follow-up. Adequately powered randomized trials are now needed to confirm these findings.