Clinical Outcomes and Quality of Life With an Ambulatory Counterpulsation Pump in Advanced Heart Failure Patients: Results of the Multicenter Feasibility Trial.

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.

The first-in-human experience with a minimally invasive, ambulatory, counterpulsation heart assist system for advanced congestive heart failure.

BACKGROUND: The intravascular ventricular assist system (iVAS) is a new, minimally invasive, ambulatory counterpulsation heart assist system delivered via the subclavian artery and powered by a portable driver. It is designed for recovery, bridge to transplantation (BTT) or for prolonging medical therapy. We report the first-in-human (FIH) experience with iVAS. METHODS: This is a prospective, non-randomized single arm, U.S. Food and Drug Administration (FDA)-approved early feasibility trial in patients listed for cardiac transplantation. The primary end-point was survival to transplant or stroke-free survival at 30 days. RESULTS: Fourteen patients were enrolled and 13 (92.8%) were treated with iVAS. At time of implant, the average age was 58 ± 6.7 years; 85% were male; 28% had ischemic cardiomyopathy; and 3 were Interagency Registry for Mechanically Assisted Devices (INTERMACS) Level 2, 9 were Level 3, and 1 was Level 4. The mean left ventricular ejection fraction was 22%, left ventricular internal diameter diastole was 7.13 mm, and 69% had moderate or severe mitral regurgitation. There were no intra-operative complications. Intensive care unit stay after implant was 6 ± 6 days. All patients were transplanted after 32 ± 21 days. There were no deaths or thromboembolic events: 1 patient required escalation of mechanical support, and post-implant complications included pleuritis/pericarditis (n = 1) and neuropathy (n = 2). No intra-operative blood transfusions were required. CONCLUSIONS: This study demonstrates a high rate of successful outcomes with an excellent risk-to-benefit profile. This FIH experience reveals that the iVAS can be successfully inserted in a standardized approach, provide hemodynamic support, can be interrupted for short periods, and allows for ambulation. A multicenter trial to investigate effectiveness and safety is warranted.

Beyond the VAD: Human Factors Engineering for Mechanically Assisted Circulation in the 21st Century.

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.

Past, present, and future regulatory aspects of ventricular assist devices.

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.

FDA's perspectives on cardiovascular devices.

The Food and Drug Administration (FDA) decision process for approving or clearing medical devices is often determined by a review of robust clinical data and extensive preclinical testing of the device. The mission statement for the Center for Devices and Radiological Health (CDRH) is to review the information provided by manufacturers so that it can promote and protect the health of the public by ensuring the safety and effectiveness of medical devices deemed appropriate for human use (Food, Drug & Cosmetic Act, Section 903(b)(1, 2(C)), December 31, 2004; accessed December 17, 2008 http://www.fda.gov/opacom/laws/fdcact/fdctoc.htm). For high-risk devices, such as ventricular assist devices (VADs), mechanical heart valves, stents, cardiac resynchronization therapy (CRT) devices, pacemakers, and defibrillators, the determination is based on FDA's review of extensive preclinical bench and animal testing followed by use of the device in a clinical trial in humans. These clinical trials allow the manufacturer to evaluate a device in the intended use population. FDA reviews the data from the clinical trial to determine if the device performed as predicted and the clinical benefits outweigh the risks. This article reviews the regulatory framework for different marketing applications related to cardiovascular devices and describes the process of obtaining approval to study a cardiovascular device in a U.S. clinical trial.

Food and Drug Administration's perspectives on pediatric cardiac assist devices.

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.