Outcomes of Impella 5.0 in Cardiogenic Shock: A Systematic Review and Meta-analysis.

OBJECTIVE: The aim of the study was to comprehensively summarize the survival outcomes and complications of Impella 5.0 (Abiomed Inc, Danvers, MA USA) use in patients with cardiogenic shock (CS). METHODS: We performed a literature review for relevant studies by searching in Medline, Medline In-Process, EMBASE, and the CENTRAL bibliographic databases on April 30, 2017. Nonoverlapping studies with 10 patients or more supported for cardiogenic shock with Impella 5.0 or Impella left direct were included. Data on patient characteristics, indication of support, and outcomes were extracted. A random effect was used to pool the various outcomes. RESULTS: This meta-analysis included six studies totaling 163 patients (mean ± SD age = 56.3 ± 12.0, male 81%). Indications for support included 88 (54.0%) for acute on chronic decompensated heart failure, 35 (21.5%) for postcardiotomy cardiogenic shock, 27 (16.6%) for acute myocardial infarction complicated by cardiogenic shock, and, 13 (8.0%) for cardiogenic shock due to other reasons. Survival to next therapy was 73.5% in patients supported for acute on chronic decompensated heart failure. The survival to device explant among patients supported for postcardiotomy cardiogenic shock or acute myocardial infarction complicated by cardiogenic shock was 90.2%, and of those, myocardial recovery was achieved in 73.8%. The overall estimated survival to discharge, 30, 180, and 365 days was 73.5%, 72.6%, 62.7%, and 58.4%, respectively. Patients supported for postcardiotomy cardiogenic shock had the highest heart recovery among survivors to explant (92.1%) and highest survival at 30 (89.5%) and 365 days (69.5%). CONCLUSIONS: Impella 5.0/LD is associated with favorable survival outcomes and higher rate of myocardial recovery in patients with cardiogenic shock.

Benefits of a novel percutaneous ventricular assist device for right heart failure: The prospective RECOVER RIGHT study of the Impella RP device.

BACKGROUND: Right ventricular failure (RVF) increases morbidity and mortality. The RECOVER RIGHT study evaluated the safety and efficacy of a novel percutaneous right ventricular assist device, the Impella RP (Abiomed, Danvers, MA), in a prospective, multicenter trial. METHODS: Thirty patients with RVF refractory to medical treatment received the Impella RP device at 15 United States institutions. The study population included 2 cohorts: 18 patients with RVF after left ventricular assist device (LVAD) implantation (Cohort A) and 12 patients with RVF after cardiotomy or myocardial infarction (Cohort B). The primary end point was survival to 30 days or hospital discharge (whichever was longer). Major secondary end points included indices of safety and efficacy. RESULTS: The patients (77% male) were a mean age of 59 ± 15 years, 53% had diabetes, 88.5% had a history of congestive heart failure, and 37.5% had renal dysfunction. Patients were on an average of 3.2 inotropes/pressors. Device delivery was achieved in all but 1 patient. Hemodynamics improved immediately after initiation of Impella RP support, with an increase in cardiac index from 1.8 ± 0.2 to 3.3 ± 0.23 liters/min/m(2) (p < 0.001) and a decrease in central venous pressure from 19.2 ± 4 to 12.6 ± 1 mm Hg (p < 0.001). Patients were supported for an average of 3.0 ± 1.5 days (range, 0.5-7.8 days). The overall survival at 30 days was 73.3%. All patients discharged were alive at 180 days. CONCLUSIONS: In patients with life-threatening RVF, the novel percutaneous Impella RP device was safe, easy to deploy, and reliably resulted in immediate hemodynamic benefit. These data support its probable benefit in this gravely ill patient population.

Endoaortic occlusion with the intraclude device during the management of ascending aortic pseudoaneurysm.

A 63-year-old man was admitted with chest pain after a previous aortic valve replacement. Computed tomographic scan identified a 7-cm pseudoaneurysm of the ascending aorta, and he was referred for repair. At operation, endoaortic occlusion of the aorta was used to arrest the heart and decompress the aorta to facilitate sternal reentry, dissection, and subsequent control. To our knowledge, this technique has not been reported and represents a useful maneuver in this challenging clinical situation.

The Impella device for acute mechanical circulatory support in patients in cardiogenic shock.

BACKGROUND: Acute cardiogenic shock is associated with high mortality rates. Mechanical circulatory devices have been increasingly used in this setting for hemodynamic support. The Impella device (Abiomed Inc, Danvers, MA) is a microaxial left ventricular assist device that can be inserted using a less invasive technique. This study was conducted to determine the outcome of patients who have undergone placement of the Impella device for acute cardiogenic shock in our institution. METHODS: A retrospective record review of 47 patients who underwent placement of the Impella device was performed from January 1, 2006, to December 31, 2011. Records were evaluated for demographics, operative details, and postoperative outcomes. Operative mortality was defined as death within 30 days of the operation. RESULTS: The patients (33 male) were an average age of 60.23 ± 13 years. The indication for placement of the Impella device included cardiogenic shock in 15 patients (32%) and postcardiotomy cardiogenic shock in 32 (68%). Of the 47 patients, 38 (80%) received the Impella 5.0 and the rest the 2.5 device. Ventricular function recovered in 34 of 47 patients (72%), and the device was removed, with 4 patients (8%) transitioned to long-term ventricular assist devices. The 30-day mortality was 25% (12 of 47 patients). Complications occurred in 14 patients (30%), consisting of device malfunction, high purge pressures, tube fracture, and groin hematoma. CONCLUSIONS: This is one of the largest series of patients undergoing placement of the Impella device for acute cardiogenic shock. Our outcomes showed improved results compared with historical data. Myocardial recovery was accomplished in most patients. Finally, the 30-day mortality and complication rate was acceptable in these critical patients. These benefits were all achieved with the Impella device in a less invasive method.

Use of the Impella 2.5 Microaxial pump for right ventricular support after insertion of Heartmate II left ventricular assist device.

The Impella microaxial pump is a catheter-based device that has been used for left ventricular support. The catheter can be inserted through a peripheral artery or directly into the ascending aorta. The pump is positioned across the aortic valve with the inflow directly in the left ventricle and the outflow in the ascending aorta. We describe the use of the Impella as a right ventricular support device during the placement of a Heartmate II left ventricular assist device. To our knowledge, this is the first report in the literature of the use of the Impella in this manner.

Outcome of the impella device for acute mechanical circulatory support.

OBJECTIVE: The contribution of cardiogenic shock to in-hospital mortality has not decreased significantly despite prompt revascularization, advances in medical therapy, and mechanical circulatory support. For patients in cardiogenic shock, mechanical circulatory support has been provided by a variety of devices. We report the outcome of the Impella device for acute mechanical circulatory support in cardiogenic shock in a setting of a large-volume single institution. The primary end points include survival to 30 days and recovery of native heart function and survival to 90 days and 1 year. The secondary end points include device complications. METHODS: We performed a retrospective chart review of 36 consecutive patients who underwent placement of the Impella device from February 6, 2006, to December 31, 2010. The charts were evaluated for data relative to the patients' demographics, hemodynamics, operative details, 30-day outcome including the patients' native heart function recovery, and 90-day and 1-year survival. RESULTS: Thirty-six consecutive patients were included in our study. The mean ± SD age was 60.3 ± 13 years, and 69% were men. The indication for placement of the Impella device included postcardiotomy cardiogenic shock in 23 patients (64%), acute myocardial infarction complicated with cardiogenic shock in 10 patients (28%), acute decompensated ischemic cardiomyopathy in 2 patients (6%), and myocarditis with cardiogenic shock in 1 patient (3%). The mean ± SD duration of the Impella support was 4.5 ± 3.9 days (range, 1-18). The 30-day survival rate was 72% (26/36), and, of those, 96% (25/26) recovered their native heart function and one (4%) was bridged to long-term left ventricular assist device (HeartMate II; Thoratec, Inc, Pleasanton, CA USA). The 90-day and 1-year survival was 64% and 61%, respectively. CONCLUSIONS: The Impella devices yielded a very favorable outcome in patients with cardiogenic shock.

The RECOVER I: a multicenter prospective study of Impella 5.0/LD for postcardiotomy circulatory support.

OBJECTIVES: Cardiogenic shock after cardiac surgery is accompanied by a high mortality rate. Early institution of hemodynamic support with a versatile, easy to insert left ventricular assist device might help bridge patients to recovery or to the next therapy, and improve the outcomes. METHODS: Patients developing cardiogenic shock or low cardiac output syndrome after being weaned off cardiopulmonary bypass were enrolled in a prospective single-arm feasibility study (RECOVER I). The primary safety endpoint was the frequency of major adverse events (death, stroke) at 30 days or discharge, whichever was longer. The primary efficacy endpoint was survival of the patient to implementation of the next therapy, which included recovery at 30 days after device removal and bridge-to-other-therapy. RESULTS: Sixteen patients provided informed consent and were enrolled in the study. Hemodynamics improved immediately after the initiation of mechanical support: cardiac index, 1.65 versus 2.7 L/min/m(2) (P = .0001); mean arterial pressure, 71.4 versus 83.1 mm Hg (P = .01); and pulmonary artery diastolic pressure, 28.0 versus 19.8 mm Hg (P < .0001). The pump provided an average of 4.0 ± 0.6 L/min of flow for an average duration of 3.7 ± 2.9 days (range, 1.7-12.6). The primary safety endpoint occurred in 2 patients (13%; 1 stroke and 1 death). For the primary efficacy endpoint, recovery of the native heart function was obtained in 93% of the patients discharged, with bridge-to-other-therapy in 7%. Survival to 30 days, 3 months, and 1 year was 94%, 81%, and 75%, respectively. CONCLUSIONS: The use of the Impella 5.0/left direct device is safe and feasible in patients presenting with postcardiotomy cardiogenic shock. The device was rapidly inserted, enabled early support, and yielded favorable outcomes.

The Swan-Ganz catheter as a teaching tool for the anesthesiologist learning minimally invasive cardiac surgery.

OBJECTIVE: To perform minimally invasive cardiac surgery through the smallest possible wound and with the least number of incisions in the heart or aorta, the necessary cannulations to undergo cardiopulmonary bypass must be done through peripheral vessels. A difficult skill to learn for the cardiac anesthesiologist is how to safely and efficiently position the coronary sinus catheter (Endoplege; Edwards Lifesciences LLC, Irvine, CA USA) required for retrograde cardioplegia administration. METHODS: In patients in whom a Swan-Ganz catheter was inserted as part of the operative management strategy for non-minimally invasive heart surgery, we have been using it as a training tool to learn how to visualize and manipulate right-sided catheters under transesophageal echocardiography. We developed this teaching technique to help hone some of the necessary skills needed to place the Endoplege catheter for minimally invasive cardiac surgery. Manipulation was done with the goal of visualizing the catheter and guiding it into the coronary sinus. For a 4-month period, anesthesia records were retrospectively reviewed. RESULTS: Fifteen patients, for a total of 19 catheter manipulations, were found in whom we had documented the use of the Swan-Ganz catheter and details about the insertion as a training tool. The coronary sinus and the catheter were visualized 100% of the time. The Swan-Ganz catheter was successfully inserted into the coronary sinus in 17 of 19 catheter manipulations. CONCLUSIONS: The Swan-Ganz catheter can be used as a training tool to develop some of the necessary skills to place catheters into the coronary sinus with transesophageal echocardiography guidance.

Real-time unconstrained object recognition: a processing pipeline based on the mammalian visual system.

The mammalian visual system is still the gold standard for recognition accuracy, flexibility, efficiency, and speed. Ongoing advances in our understanding of function and mechanisms in the visual system can now be leveraged to pursue the design of computer vision architectures that will revolutionize the state of the art in computer vision.

Structure stability/activity relationships of sulfone stabilized N,N-dichloroamines.

Structure stability/activity relationships (SXR) of a new class of N,N-dichloroamine compounds were explored to improve antimicrobial activity against Escherichia coli, Staphylococcus aureus, and Candida albicans while maintaining aqueous solution stability. This study identified a new class of solution-stable and topical antimicrobial agents. These agents are sulfone-stabilized and possess either a quaternary ammonium or sulfonate appendages as a water solubilizing group. Several unique challenges were confronted in the synthesis of these novel compounds which are highlighted in the discussion.

Novel N-chloroheterocyclic antimicrobials.

Antimicrobial compounds with broad-spectrum activity and minimal potential for antibiotic resistance are urgently needed. Toward this end, we prepared and investigated a novel series of N-chloroheterocycles. Of the compounds examined, the N-chloroamine series were found superior over N-chloroamide series in regards to exhibiting high antimicrobial activity, low cytotoxicity, and long-term aqueous stability.

Novel 3-chlorooxazolidin-2-ones as antimicrobial agents.

Antimicrobial resistance against many known therapeutics is on the rise. We examined derivatives of 3-chlorooxazolidin-2-one 1a (X=H) as antibacterial and antifungal agents. The key findings were that the activity and apparent in vitro cytotoxicity could be controlled by the substitution of charged solubilizers at the 4- and 5- positions. These changes both significantly increase the antifungal potency and decrease cytotoxicity. Particularly effective were trialkylammonium groups which led to 400- to 600-fold increases in the antifungal therapeutic index when compared to their unsubstituted counterparts.

Edwards EndoVent as a pacing catheter for minimally invasive aortic valve surgery: a novel approach.

OBJECTIVE: The placement of epicardial pacing wires before weaning from bypass during port-access heart surgery can be difficult or impossible. Sometimes, it is necessary to pacing the patient to wean from bypass, and it is problematic to exchange the Edwards pulmonary vent (EndoVent) for a pace catheter under the drapes. Our objective was to devise an effective means of pacing the patient using the pulmonary vent catheter. METHODS: All patients having aortic valve minimally invasive port-access surgery have a pacing wire deployed through the Edwards EndoVent catheter. We did a retrospective chart analysis of these cases. RESULTS: After reviewing the anesthesia records, we determined that we were able to reliably convert the pulmonary vent catheter, which is beneficial for the surgery, into a pacing catheter before weaning from bypass 100% of the time. The mean pacing threshold current was 1.60 mA with the wire in the right ventricular apex. CONCLUSIONS: We found that in all 25 patients we were able to rapidly convert the vent catheter into a reliable pacing catheter without any complications.

Insertion of the Impella 5.0 left ventricular assist device via right anterior mini-thoracotomy: a novel practical approach.

The Impella 5.0 microaxial pump is a miniaturized left ventricular assist device commonly used for circulatory support in acute cardiogenic shock. The catheter-based pump is designed to be inserted either into a peripheral artery or directly into the ascending aorta. We report the first case in which the Impella 5.0 device was placed directly into the ascending aorta via a small right anterior thoracotomy in a patient following acute myocardial infarction complicated by cardiogenic shock.

Discovery of N-methyl-4-(4-methoxyanilino)quinazolines as potent apoptosis inducers. Structure-activity relationship of the quinazoline ring.

As a continuation of our efforts to discover and develop apoptosis inducing N-methyl-4-(4-methoxyanilino)quinazolines as novel anticancer agents, we explored substitution at the 5-, 6-, 7-positions of the quinazoline and replacement of the quinazoline by other nitrogen-containing heterocycles. A small group at the 5-position was found to be well tolerated. At the 6-position a small group like an amino was preferred. Substitution at the 7-position was tolerated much less than at the 6-position. Replacing the carbon at the 8-position or both the 5- and 8-positions with nitrogen led to about 10-fold reductions in potency. Replacement of the quinazoline ring with a quinoline, a benzo[d][1,2,3]triazine, or an isoquinoline ring showed that the nitrogen at the 1-position is important for activity, while the carbon at the 2-position can be replaced by a nitrogen and the nitrogen at the 3-position can be replaced by a carbon. Through the SAR study, several 5- or 6-substituted analogs, such as 2a and 2c, were found to have potencies approaching that of lead compound N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine (1g, EP128495, MPC-6827, Azixa).

Discovery of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine, a potent apoptosis inducer and efficacious anticancer agent with high blood brain barrier penetration.

As a continuation of our structure-activity relationship (SAR) studies on 4-anilinoquinazolines as potent apoptosis inducers and to identify anticancer development candidates, we explored the replacement of the 2-Cl group in our lead compound 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (6b, EP128265, MPI-0441138) by other functional groups. This SAR study and lead optimization resulted in the identification of N-(4-methoxyphenyl)-N,2-dimethylquinazolin-4-amine (6h, EP128495, MPC-6827) as an anticancer clinical candidate. Compound 6h was found to be a potent apoptosis inducer with EC(50) of 2 nM in our cell-based apoptosis induction assay. It also has excellent blood brain barrier penetration, and is highly efficacious in human MX-1 breast and other mouse xenograft cancer models.

Triterpene based compounds with potent anti-maturation activity against HIV-1.

Efforts towards developing orally bioavailable HIV-1 maturation inhibitors starting from betulinic acid 1 are described. SAR resulted in improved potency, physicochemical properties, and enhanced oral absorption in rats.

Discovery of 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine (EP128265, MPI-0441138) as a potent inducer of apoptosis with high in vivo activity.

Using a live cell, high-throughput caspase-3 activator assay, we have identified a novel series of 4-anilinoquinazolines as inducers of apoptosis. In this report, we discuss the discovery of 2-chloro-N-(4-methoxyphenyl)-N-methylquinazolin-4-amine, compound 2b (EP128265, MPI-0441138) as a highly active inducer of apoptosis (EC50 for caspase activation of 2 nM) and as a potent inhibitor of cell proliferation (GI50 of 2 nM) in T47D cells. Compound 2b inhibited tubulin polymerization, was effective in cells overexpressing ABC transporter Pgp-1, and was efficacious in the MX-1 human breast and PC-3 prostate cancer mouse models. In contrast to the SAR of 4-anilinoquinazolines as EGFR kinase inhibitors, the methyl group on the nitrogen linker was essential for the apoptosis-inducing activity of 4-anilinoquinazolines and substitution in the 6- and 7-positions of the quinazoline core structure decreased potency.

Improving outcomes in patients with ventricular assist devices transferred from outlying to tertiary care hospitals.

In this retrospective study, the implant course and outcome of patients with ventricular assist devices (VADs) transferred from outlying "spoke" hospitals and converted nonsurgically to a device designed for ambulation at tertiary care "hub" hospitals are evaluated. Factors affecting the crucial decision to transfer and to convert devices have not previously been characterized. Data from 50 patients at 26 US hub institutions were voluntarily submitted to a VAD data registry at ABIOMED, between December 2003 and December 2005. The patients were transferred from 40 spokes on the BVS 5000 Blood Pump and converted to the AB5000 Ventricle (both ABIOMED) at hubs. Comparisons were made on implant indications, time-course, and end-organ function at the time of conversion between surviving patients and patients that had died. Patients who were transferred and converted had a survival to recovery or to next therapy rate of 42%. Eighteen of the surviving patients were still alive 30 days after the explant: 61% were weaned, 33% were transplanted, and 5.6% received a destination device. Average implant-to-transfer time was 1.5 vs. 2.0 days for 30-day survivors and expired patients, respectively, whereas support time from transfer to conversion was 4.8 vs. 4 days, respectively. At the time of device conversion, a total bilirubin below a threshold level of 3.5 mg/dL was predictive of 30-day survival (n = 26, p = .03, odds ratio = 2.73, 95% confidence interval: 1.22-6.16). Patients who survived 30 days were supported longer than those who died (35 vs. 21.1 days, p = .026). At least 18 patients recovered sufficiently on the AB5000 Ventricle to tolerate extubation and 11 patients were able to ambulate. Liver function after implant both at the spoke and before conversion at the hub may be a good indicator of patient survivability. Patients transferred from the BVS 5000 Blood Pump benefited from easy, safe conversion to the AB5000 Ventricle, which provided them with additional support time and afforded the opportunity to recover native heart function.