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Background: The NuPulseCV intravascular ventricular assist system (iVAS) provides extended duration ambulatory counterpulsation via a durable pump placed through the distal subclavian artery. Methods: We performed a prospective, single-arm, multicenter, US Food and Drug Administration-approved feasibility trial of iVAS therapy as a bridge to transplant or decision following the FIH (First-In-Human) trial. Results: Forty-seven patients were enrolled, and 45 patients (median 61 years old, 37 males, and 30 listed on United Network of Organ Sharing) received iVAS support for median 44 (25–87) days. There were no intraoperative complications. Success was defined as survival or transplant on iVAS therapy free from disabling stroke. Outcome success at 30 days (the primary end point of this study) and at 6 months was 89% and 80%, respectively. During 6 months of iVAS support, 2 patients died and 2 patients experienced disabling neurological dysfunction. Six-minute walk distance, 2-minute step test, and Kansas City Cardiomyopathy Questionnaire score improved during 4-week iVAS support. Conclusions: This feasibility trial demonstrated promising short-term outcomes of iVAS therapy with improved functional capacity and quality of life during the therapy. Registration: URL: http://www.clinicaltrials.gov . Unique identifier: NCT02645539.

Summary of Objectives This is a single-arm, non-randomized study designed to assess the preliminary safety and clinical performance of a novel ambulatory counterpulsation device. The device is an intra-aortic, counterpulsation blood pump delivered via axillary artery. The system includes a skin interface device facilitating patient ambulation and an external, portable drive unit allowing increased mobility and independence. This study will assess potential benefits to patients who have advanced heart failure and require additional circulatory support. This study will evaluate human factors, the clinical safety of the device, device failures, whether the device performs its intended purpose, patient characteristics that may impact device performance, and device use outside of the hospital. Methods Following a First-in-Human study of 14 patients, this feasibility study will enroll up to 86 implanted patients in up to 20 investigational sites for a total of 100 patients on device. To date, 71 of 100 patients have been implanted across 14 of 16 participating institutions. Endpoints The primary endpoint of this study is to assess survival to transplant or stroke-free survival at 30 days. The following secondary endpoints will also be evaluated at 30 days: number of patients who deteriorate requiring escalation of inotropic support and/or additional mechanical circulatory support; incidence of serious device-related adverse events; incidence of procedure-related adverse events; incidence of all adverse events; change in NYHA class from baseline; change in quality of life from baseline as measured by Kansas City Cardiomyopathy Questionnaire (KCCQ) - global assessment; change in Seattle Heart Failure Model Prognosis Score; change in six minute walk test and two minute step test from baseline. Subjects supported with the device past 30 days will continue to be followed and evaluated in the study until transplantation, device explant, alternative mechanical circulatory support or death. A Pivotal Trial with this device is expected to begin by the second quarter of 2020.

Thousands of ventricular assist devices (VADs) currently provide circulatory support to patients worldwide, and dozens of heart pump designs for adults and pediatric patients are under various stages of development in preparation for translation to clinical use. The successful bench-to-bedside development of a VAD involves a structured evaluation of possible system states, including human interaction with the device and auxiliary component usage in the hospital or home environment. In this study, we review the literature and present the current landscape of preclinical design and assessment, decision support tools and procedures, and patient-centered therapy. Gaps of knowledge are identified. The study findings support the need for more attention to user-centered design approaches for medical devices, such as mechanical circulatory assist systems, that specifically involve detailed qualitative and quantitative assessments of human-device interaction to mitigate risk and failure.

Purpose The intravascular ventricular assist system (iVAS) is a minimally invasive, ambulatory, counterpulsation heart assist system that is inserted through the subclavian artery and sits in the descending aorta. It has been evaluated in a feasibility trial with expanded indications to include patients who were a bridge to decision (BTD). The objective was to evaluate the role of iVAS as a BTD device. Methods As part of a multicenter US FDA approved feasibility trial, 13 of 44 patients were implanted with iVAS as a BTD. Patients were in advanced congestive heart failure (CHF), did not have an irreversible contraindication to transplant, and were not listed at the time of implantation. Results Four patients were bridge to candidacy (BTC) due to substance abuse - three received a transplant and one is still in a probationary period. Two patients were Jehovah's Witnesses who needed their anemia and end organ function to improve prior to escalation of therapy. Both had comorbidities that precluded transplant and they received a left ventricular assist device (LVAD). One patient was implanted for recovery but the anatomy of his aorta proved incompatible with an iVAS and he received a LVAD. Two patients were initially too frail to receive a LVAD or transplant - one improved and received a transplant and the other is ongoing as a BTC. Two patients received an iVAS for intractable angina. One patient had transplant arteriopathy but also had severe peripheral vascular disease that precluded transplant. The iVAS was explanted after a year and symptom improvement. The other patient had nonrevascularizable coronary disease and had relief of his angina but died suddenly at home from an unknown cause. Two patients had cardiogenic shock after myocardial infarction and were supported for over 6 months. The average duration of iVAS support was 129 ± 101 days. At the time of iVAS implant, 8/13 patients had contraindications to LVAD. At 6 months, 11/13 had been successfully supported with iVAS and reached the intended goal. Conclusion The utility and versatility of the iVAS as a BTD was demonstrated in this trial. Outcomes were excellent in very challenging patients, many with contraindications for LVADs. The iVAS allowed a variety of patients time to improve their physical condition and transplant candidacy and is an important adjunct in treating complex advanced CHF patients.

Purpose The intravascular ventricular assist system (iVAS) is a long-term, ambulatory counterpulsation heart assist system designed for long term use in patients with advanced congestive heart failure (aCHF). A feasibility trial has been conducted and early analysis showed several pre-implant parameters, particularly cardiac power efficiency (CPE), could predict hemodynamic success. The data has been reanalyzed with completion of the trial. Methods A multicenter, US FDA approved feasibility trial enrolled 44 patients with aCHF to receive the iVAS device as a bridge to transplant or decision. Hemodynamic parameters, including CPE, were collected pre-implantation. CPE is defined as the cardiac power index (CPI) divided by the pulmonary capillary wedge pressure (PCWP). Patients were optimized with inotropes or intra-aortic balloon pumps (IABP). Patients had hemodynamic success (HS) if they were weaned off inotropes and had clinically acceptable hemodynamics. The success (HS) and non-success (NHS) groups were compared. Results Demographics were as follows: the average age was 58.9 ± 7.7, 82% were male, 48% had ischemic cardiomyopathy, the mean pre-operative left ventricular ejection fraction was 23.6 ± 10.7, and 86% were on inotropes and/or an IABP. HS was achieved in 30 patients, 69.8%, with 13 NHS patients, 30.2%. Table 1 displays pre-implant hemodynamics in both groups. While many parameters differed between groups, the most predictive parameter was CPE with an area under the receiver operator curve of 0.986. A CPE cutoff of ≥ 0.0175 has a sensitivity of 92.6% and specificity of 100%. Conclusion Cardiac reserve is required for a counterpulsation device to be effective. This study further supports the use of CPE as a very accurate predictor of hemodynamic success with the iVAS device. This parameter combines power and preload to better assess a patient's cardiac reserve and improve patient selection.

Purpose The NuPulseCV intravascular ventricular assist system (iVAS) provides extended duration ambulatory counterpulsation and can be used for subacute or chronic cardiac support. The pump consists of a durable 50cc counterpulsation pump placed through the subclavian artery, and a transcutaneous electromechanical conduit for air and electrocardiographic data transmission. Previously, we reported on the First in Human (FIH) experience of the iVAS in 14 patients, focusing on the implantation technique, outcomes and complications. Hereby, we are reporting the results of the iVAS feasibility study in advanced heart failure (aCHF) patients. Methods This is a prospective, non-randomized single arm trial of iVAS implantation in aCHF patients eligible for cardiac transplantation. The primary endpoint was transplant or survival at 30 days; secondary endpoints include procedural success, adverse events, exercise performance and quality of life during device support. Results Forty-six patients were enrolled and 44 received iVAS. There were 36 males; mean age 58.9±7.7 years; cardiomyopathy ischemic 21 and non-ischemic 23; 98% were NYHA 3-4; 98% were INTERMACS 2-4; LVEF 23.6±10.7. 88.6% of patients successfully achieved the primary endpoint. Six minute walk improved by 23% from 1011±300 to 1234±360 2-4 weeks after implant. Kansas City Cardiomyopathy scores improved from 49 to 61. 16 patients were discharged home with iVAS support. Conclusions In this feasibility trial, using iVAS in aCHF patients eligible for heart transplantation, we demonstrated high rate of achieving the primary endpoint success with excellent procedural success and significant improvement in exercise performance and quality of life parameters. These data, along with those from a current trial enrolling a wider range of aCHF patients regardless of transplant eligibility, will be used to support initiation of a pivotal study.

The development of ventricular assist devices (VADs) for the treatment of heart failure has been ongoing since the National Heart Lung and Blood Institute (NHLBI) initiated the artificial heart program in 1964. The primary goal was to develop VADs and total artificial hearts for both temporary (short-term) and long-term use. Due to a small target population and the inability to blind patients and clinicians, the Food and Drug Administration (FDA) has recognized the challenges of conducting trials with these invasive devices. In an effort to address those challenges, FDA has accepted a variety of clinical trial designs to collect the data required to evaluate safety and effectiveness data in different patient groups. This article will provide a detailed discussion of the past, present, and future FDA regulatory considerations for VADs.

Dual missions of the Center for Devices and Radiological Health at the Food and Drug Administration (FDA) are 1) promoting public health by promptly reviewing and taking appropriate, timely action regarding the marketing of regulated medical devices while at the same time, and 2) protecting public health by ensuring a reasonable assurance of the safety and effectiveness of medical devices deemed appropriate for human use. In the past, clinicians have used cardiac assist devices intended for adults to treat pediatric heart failure patients. However, because of the larger size of the approved devices, many pediatric patients are underserved by this approach. Currently, several cardiac assist devices intended for use in pediatric patients are being developed. FDA believes that clinical data used to support such safety and probable benefit may be derived from a small focused clinical trial in this target population, and developers may want to consider this approach for approval of the humanitarian device exemption application. Pediatric device development is challenging and early communication with FDA to develop an appropriate regulatory and scientific pathway for device submission is advised and warranted. This early interaction can facilitate the development of a small but necessary trial for these life-sustaining pediatric cardiac assist devices.