Ambulatory Counterpulsation Research Articles

P20: Development and Testing of an External Electro-pneumatic Device For Ambulatory Counterpulsation

Purpose: The NuPulse iVAS is a minimally invasive, portable, counterpulsation platform technology that provides ambulatory circulatory support. iVAS successfully supported 81 patients in an FDA-approved feasibility trial. iVAS required implantation of a Skin Interface Device (SID 1.0, 69 mm diameter) with a large exit site (22 mm diameter) and subcutaneous ECG leads. SID 1.0 implantation required two incisions and creation of a large subcutaneous pocket (excluding small and pediatric patients) which could be obviated by an external SID. Methods: To reduce iVAS invasiveness and implant time, NuPulse redesigned the SID (SID 2.0) to be external (9.5 x 5.0 x 3.5 cm, 100 g) with surface ECG leads. The performance of SID 2.0 was compared to SID 1.0 through bench testing to regulatory standards. Results: SID 2.0 enables reduction in surgical time by 90 min, and atraumatic replacement. The pneumatic driveline exit site diameter was reduced to 5 mm (~500% reduction in area). SID 2.0 provided similar ECG microprocessing speed and results with surface ECG as the SID 1.0 with subcutaneous ECG leads. SID 2.0 is worn in a device belt, and passed human factors testing for surface ECG lead wire management and hand-free support for SID 2.0. Summary: Clinical trial experience with SID 1.0 drove design modifications to system components. The NuPulse portable counterpulsation platform will have an external SID 2.0 which improves patient safety and patient experience, while reducing surgical time and invasiveness.

Abstract 13753: Early and Late Outcomes of Ambulatory Counter Pulsation Device: Novel Intravascular Ventricular Assist Device vs Conventional Axillary Intra-aortic Balloon Pump

Introduction: Intravascular ventricular assist device (iVAS; NuPulse CV, North Carolina, USA) is a newly developed ambulatory and portable counter pulsation heart assist system. Hypothesis: Early and late clinical outcomes of iVAS is comparable to those of conventional axillary intra-aortic balloon pump (IABP) as a bridge to heart transplantation(BTT). Methods: Between April 2016 and January 2020, 33 patients underwent iVAS implantation (Group A) and 69 patients underwent axillary IABP (Group B) as a BTT. We reviewed perioperative data and late clinical outcomes including survival. Long-term survival was assessed with the Kaplan-Meier analysis. Results: The patients in Group A was significantly older than Group B (A: 58.8±8.1 vs B: 53.3±14.7 p=0.048). The use of inotropes at the time of device implantation was similar between two groups (A:22/33(66.7%) vs B: 47/69(68.1%), p=0.88). Almost all patients were able to ambulate and participate in physical therapy (A:100% vs B:97.1%, p=0.21). The duration of device support in Group A was significantly longer than Group B (A:83.3±93.7 vs B:19.0±13.3 days, p <0.01). After a FDA approval, eleven patients (44%) in Group A was able to be discharged with an iVAS. While waiting for transplantation, 3 patients expired in Group A and none in Group B. Two patients in Group A required an escalation of support (ECMO N=1, LVAD N=1) and 1 patients in Group B (percutaneous LVAD N=1). Balloon exchange due to device related complications was required less frequently in Group A compared to Group B (A: 2/33, 6.1% vs B: 20/69, 29.0% p <0.01). Adverse events during balloon exchange included aortic rupture (N=1) and type A aortic dissection (N=1) (all in Group B). The success rate of BTT was not significantly different between groups (A:27/32(84.4%), B: 64/68(94.1%),p=0.13). The long-term survival after heart transplantation did not differ between the groups (A: 78.1% at 3 years vs B: 83.8% at 3 years, log-rank=0.07). Conclusions: Both iVAS and conventional axillary IABP showed comparable long-term survival and decent success rates of BTT. The iVAS featured with the portable mechanism might be a promising option as a BTT.

NuPulse or No Pulse: VT Ablation in A Patient with The NuPulse Ivas Device

Introduction The intravascular ventricular assist system (iVAS) is the first minimally invasive, long-term, ambulatory counter-pulsation device that is currently being investigated as a bridge-to-transplant option for patients with advanced heart failure (HF). Ventricular tachycardia (VT) is a common complication in patients with advanced HF. Catheter ablation with substrate modification is an effective management strategy. We describe, to the best of our knowledge, the first reported case of VT ablation in a patient with the NuPulse iVAS device. Case An 82-year-old male came to the ED as his defibrillator discharged 4 times over 48 hours. He had a past history of ACC/AHA Stage D HFrEF (EF of 35%) due to ischemic cardiomyopathy. Given his advanced HF, he was enrolled in the iVAS trial and was implanted in 2019. On arrival, his BP was 172/99 mmHg and HR was 114/min. He was mildly hypervolemic on exam. CXR revealed mild pulmonary vascular congestion (Fig. 1B). ECG showed VT with a rate of 120/min (Fig. 1A). He was given IV procainamide, which transiently converted him to his baseline ventricular-paced rhythm, and his ICD was re-programmed to pace-terminate VT > 102/min. He was then loaded with IV lidocaine. Yet, he continued to have runs of VT. The next day, he underwent an adenosine nuclear stress test which showed a large severe fixed defect in the inferior and inferolateral regions suggestive of scar (Fig 1C). The following day, he underwent a VT ablation. A trans-septal approach was used to enter the LV and the scar was mapped (Fig 1D & E). Interestingly, every time radiofrequency ablation was delivered, there was electromagnetic interference with the iVAS device ECG leads which caused it to turn off. The patient became hypotensive during these episodes and dobutamine was used intra-procedurally for ionotropic support. Ablation was delivered in short bursts to allow the iVAS device to function intermittently, which prolonged the procedure time. The patient tolerated the procedure well and he has not had any recurrent VT. Discussion Long term mechanical circulatory support devices are an exciting emerging field. Complications of advanced HF include VT which is often difficult to control with medication alone and benefits from ablation. However, it appears that electromagnetic interference from radiofrequency ablation delivery impairs function of the iVAS ECG leads which gate the inflation & deflation of the counter-pulsation balloon to the cardiac cycle. Future iterations of the device must consider alternative triggers, such as being able to connect the device's ECG input to surface electrodes which would not be compromised during ablation delivery.

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

The NuPulseCV intravascular ventricular assist system (iVAS) provides extended duration ambulatory counterpulsation via a durable pump placed through the distal subclavian artery. 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. 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. 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.

A Clinical Study to Evaluate Ambulatory Counterpulsation for the Treatment of Advanced Heart Failure: A Feasibility Study

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. 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. 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.

Cardiac Reserve as Assessed by Augmentation in Cardiac Power Efficiency Predicts Response to Intravascular Ventricular Assist System Support

The intravascular ventricular assist system (iVAS) is a durable, ambulatory counterpulsation device that is currently under investigation for advanced heart failure patients. Baseline cardiac power efficiency (CPE) has previously been reported to predict hemodynamic success after iVAS. We investigated the role of change in CPE after inotropic challenge, a marker of cardiac reserve, as a prognostic tool prior to iVAS support. Hemodynamic data at the time of right heart catheterization was collected on patients just prior to iVAS implantation. A subset of patients underwent milrinone loading followed by repeat hemodynamic assessment 10 min after a 50 mcg/kg milrinone infusion. Cardiac power index (CPI) was calculated as [CPI = cardiac index (CI) x mean arterial pressure (MAP)/451)] and CPE was calculated as [CPE = CPI/Pulmonary capillary wedge pressure (PCWP)]. CPE at baseline and after inotropic challenge was calculated and a percent augmentation of 25% or greater in CPE was used as a cutoff indicative of cardiac reserve. The combined endpoint of independently adjudicated heart failure events, dependency on inotropes 7 days after implant, need for escalation to ECMO or death was evaluated. 40 patients from a single institution underwent iVAS implantation. 39 patients underwent RHC prior to iVAS (11.7 +/- 14.0 days before surgery). 11 patients underwent milrinone loading followed by repeat hemodynamic assessment. Baseline hemodynamics revealed an average CPE of 0.0227 +/- 0.0148 watts*mmHg/m2 for the entire cohort. In the subset of patients who underwent milrinone loading, CPE increased on average 41% from 0.0141 +/- 0.0055 watts*mmHg/m2 to 0.0236 +/- 0.0114 watts*mmHg/m2 (p = 0.003). There was a trend towards freedom from death, ECMO, HF events, or inotrope dependency in those who were able to augment CPE by more than 25% (N = 8), compared to those with less (N = 3) cardiac reserve OR = 0.071 (95% CI 0.003 - 1.73, p = 0.105). Cardiac reserve as defined as a greater than 25% augmentation in CPE after milrinone challenge may predict future success with counterpulsation with iVAS. This hypothesis generating question warrants further investigation.

An ambulatory counterpulsation system-a potential option for extended mechanical support.

As the incidence of heart failure increases, an organ shortage for cardiac transplant worsens. There has been development of both short and long-term mechanical circulatory devices for this population, each with unique advantages and different adverse event profiles. The long-term devices provide excellent mechanical circulatory support but are associated with significant morbidity. The intravascular ventricular assist system (iVAS) is a minimally invasive, ambulatory, counterpulsation heart assist system developed to provide long-term support for patients with advanced heart failure while avoiding the surgical trauma of a left ventricular assist device and minimizing the risks of infection and hemocompatibility-related adverse events. Initial experience with the iVAS shows promising evidence for its use as a long-term mechanical circulatory support device.

Hemodynamic Parameters That Predict Success with an Ambulatory Counterpulsation Heart Assist System in Advanced Congestive Heart Failure

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.

Improvement in Biventricular Cardiac Function After Ambulatory Counterpulsation

The NupulseCV intravascular ventricular assist system (iVAS), which consists of a durable pump placed through the subclavian artery, provides extended-duration ambulatory counterpulsation. This study investigated the effect of iVAS on biventricular cardiac function. We reviewed all heart failure patients who received iVAS implantation as a bridge to transplantation or a bridge to candidacy since April 2016 as part of the iVAS first-in-humans and subsequent feasibility study. We compared data of transthoracic echocardiography performed just before implantation (without iVAS support) and again at 30 days or just before explantation (on iVAS support). Eighteen patients (58.8 ± 7.4 years old and 15 male) received iVAS support for 53 ± 43 days. Fourteen patients were bridged to cardiac replacement therapy after 35 ± 19 days and the remaining 4 patients had been supported for 118 ± 41 days. There were no deaths during iVAS support. At 30 days, there was a significant improvement in left ventricular ejection fraction (16.5% ± 11.9% vs 24.4% ± 12.8%; P = .007) and marked reduction in left atrial size (62.7 ± 35.7 mL/m2 vs 33.8 ± 17.2 mL/m2; P < .001). Right ventricular fractional area change improved dramatically (25.4% ± 12.9% vs 42.1% ± 12.4%; P < .001). All other right ventricular and right atrial parameters improved significantly as well (size, tricuspid annular plane systolic excursion, and velocity of tricuspid annular systolic motion). Improvement in biventricular cardiac function was observed after 30 days of iVAS support. Further studies should examine the use of this technology as a bridge to recovery.

Clinical Outcome and Quality of Life with an Ambulatory Counterpulsation Pump (iVAS) in Advanced Heart Failure Patients

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.

Ambulatory Counter Pulsation at Home- A Dream that Became a Reality

The NuPulseCV intravascular assist system (iVAS) is an ambulatory counterpulsation device with a portable drive unit. This device permits patients to be discharged home. The purpose of this study was to assess the outcomes of patients in the NuPulseCV First-In-Human and Feasibility clinical trials who were discharged home following iVAS implantation.

Ambulatory Counterpulsation with a Minimally Invasive Circulatory Assist Device - Expanding Indications and Extending Support

Ambulatory Counterpulsation with a Minimally Invasive Circulatory Assist Device - Expanding Indications and Extending Support

Reverse Remodeling Following Ambulatory Counterpulsation

Reverse Remodeling Following Ambulatory Counterpulsation

Predictors of Hemodynamic Success in Advanced CHF Patients Supported by Ambulatory Counterpulsation

The NuPulseCV iVAS is a minimally invasive, ambulatory, 50cc counterpulsation device. It provides extended duration support for advanced CHF(aCHF) patients. It is unknown which aCHF patients would respond favorably to counterpulsation. We, therefore, reviewed the early clinical iVAS trial data to determine which pre-implant parameters could predict hemodynamic success.

Hemocompatibility of an Ambulatory Counterpulsation Circulatory Assist System

Hemocompatibility of an Ambulatory Counterpulsation Circulatory Assist System

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

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. 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. 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. 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.