The gas-line and lead were connected to the “Y” connector of the PIL, which was tunneled under the rectus sheath to an exit site located on the abdomen. A driver was attached to the patient connector

and a programmer was used to adjust cuff inflation volume and timing of inflation and deflation in relation to the cardiac cycle to optimize the counterpulsation effect (Figure 1B). Balloon inflation was timed via the programmer to begin right after the dicrotic notch, while deflation started during the pre-ejection phase and continued during the ejection phase of systole in such a way that 70 ± 10% of the balloon ATM signaling pathway was deflated at the start of ejection. Patients were discharged from the hospital once heart failure medications were re-established and the patients were ambulatory and able to demonstrate the ability to care for the exit site and manage the driver. Patients were scheduled to be seen by the heart failure clinician-investigator and study coordinator at 1, 3, 6, and 12 months post-implant. During the primary period of follow-up (the first 6 MAPK inhibitor months), the C-Pulse System was intended to be used at least 20 h per day.

The non–blood contacting feature of the C-Pulse System allows the device to be intermittently turned off as tolerated. This enables the patient to be “untethered” from the device, allowing freedom for personal hygiene and convenience. Follow-up visits included a repeat of baseline tests: physical examination, medication summary, and assessment of NYHA functional class, QoL as measured by the Minnesota Living with Heart Failure questionnaire and the Kansas City Cardiomyopathy Questionnaire, 6MWD, and pVO2 (repeated at 6 months only). Safety data, including adverse events, was collected continuously. The CT was repeated at 6

months only. Data were collected via electronic data capture screens referred to as e-case report forms and independently monitored. Core laboratories were used to provide data on CT scans (Cardiovascular Core Labs, Washington, DC), echocardiograms (Cardiovascular Core Labs, Washington, DC), and pVO2 testing (Henry SDHB Ford Health System, Detroit, Michigan). Functional status assessments and QoL testing (NYHA functional classification and QoL scoring, respectively) were conducted using standardized and validated approaches and questionnaires 1 and 17. Adverse events were recorded by the clinical sites and adjudicated by an independent Clinical Events Committee (see the Online Appendix). Adverse event definitions were based on Version 2.2 adverse event definitions for the Intermacs registry 2 and 18. This feasibility study was designed to assess the safety and potential benefit of the C-Pulse System in patients with NYHA functional class III-ambulatory functional class IV heart failure. As with most Investigational Device Exemption feasibility studies, the primary focus of the U.S.