Robert D. Dowling

Proof of concept: hemodynamic response to long-term partial ventricular support with the synergy pocket micro-pump

OBJECTIVESnThe purpose of this study was to test the hemodynamic effects of partial ventricular support in patients with advanced heart failure.nnnBACKGROUNDnThe use of current left ventricular assist devices (VADs) that provide full circulatory support is restricted to critically ill patients because of associated risks. Smaller, less-invasive devices could expand VAD use to a larger pool of less-sick patients but would pump less blood, providing only partial support.nnnMETHODSnThe Synergy Pocket Micro-pump device (CircuLite, Inc., Saddle Brook, New Jersey) pumps approximately 3.0 l/min, is implanted (off pump) via a mini-thoracotomy, and is positioned in a right subclavicular subcutaneous pocket (like a pacemaker). The inflow cannula inserts into the left atrium; the outflow graft connects to the right subclavian artery.nnnRESULTSnA total of 17 patients (14 men), age 53 +/- 9 years with ejection fraction 21 +/- 6%, mean arterial pressure 73 +/- 7 mm Hg, pulmonary capillary wedge pressure 29 +/- 6 mm Hg, and cardiac index 1.9 +/- 0.4 l/min/m(2) received an implant. Duration of support ranged from 6 to 213 (median 81) days. In addition to demonstration of significant acute hemodynamic improvements in the first day of support, 9 patients underwent follow-up right heart catheterization at 10.6 +/- 6 weeks. These patients showed significant increases in arterial pressure (67 +/- 8 mm Hg vs. 80 +/- 9 mm Hg, p = 0.01) and cardiac index (2.0 +/- 0.4 l/min/m(2) vs. 2.8 +/- 0.6 l/min/m(2), p = 0.01) with large reductions in pulmonary capillary wedge pressure (30 +/- 5 mm Hg vs. 18 +/- 5 mm Hg, p = 0.001).nnnCONCLUSIONSnPartial support appears to interrupt the progressive hemodynamic deterioration typical of late-stage heart failure. If proven safe and durable, this device could be used in a relatively large population of patients with severe heart failure who are not sick enough to justify use of currently available full support VADs. (Safety and Performance Evaluation of CircuLite Synergy; NCT00878527).

Improved pain control after cardiac surgery: results of a randomized, double-blind, clinical trial

OBJECTIVEnWe sought to determine whether a continuous regional infusion of a local anesthetic delivered to the operative site would result in decreased levels of postoperative pain and narcotic requirements for patients who undergo a standard median sternotomy for cardiac surgery.nnnMETHODSnA double-blind, randomized, controlled trial was conducted at a single center. Patients who were undergoing elective coronary artery bypass graft surgery alone or combined with laser transmyocardial revascularization received bilateral intercostal nerve blocks with either ropivacaine or saline. At wound closure, 2 catheters with multiple side openings were inserted percutaneously and placed directly over the sternum. The same agent (ropivacaine vs saline) was then administered as a continuous regional infusion for 48 hours through an elastomeric pump. Requirements for postoperative systemic narcotic analgesics and pain assessment scores were recorded for 72 hours after the operation. Secondary outcome measures were hospital length of stay and pulmonary function test results. Pain scores and narcotic use on the second postoperative day were also compared to avoid the confounding influence of anesthesia administered at the time of the operation.nnnRESULTSnThe total amount of narcotic analgesia required by the ropivacaine group was significantly less than that of the control group (47.3 vs 78.7 mg, respectively; P =.038). The ropivacaine group required less narcotics on postoperative day 2 as well (15.5 vs 29.4 mg, P =.025). The mean overall pain scores for the ropivacaine group were significantly less than the mean overall scores for the normal saline group (1.6 vs 2.6, respectively; P =.005). Patients receiving ropivacaine had a mean length of stay of 5.2 days compared with 8.2 days for patients in the normal saline group (P =.001). Excluding the data from outliers (length of stay = 39 days), the normal saline group mean length of stay was 6.3 days (P <.01). There was no difference in assessment of pulmonary function.nnnCONCLUSIONnContinuous delivery of local anesthetics significantly improved postoperative pain control while decreasing the amount of narcotic analgesia required in patients who underwent standard median sternotomy. There was also a significant decrease in hospital length of stay, which is likely to result in significant cost reductions.

The AbioCor implantable replacement heart

The AbioCor implantable replacement heart (IRH) is the first available totally implantable artificial heart. We recently initiated a multicenter trial of this device in patients with severe, irreversible biventricular failure. Patients who were not candidates for other therapies, including transplantation, were evaluated. All candidates were adults with inotrope-dependent biventricular failure, whose 30-day predicted mortality was higher than 70%. A three-dimensional computerized fit study predicted fit of the AbioCor thoracic unit in all recipients. At operation, the internal battery controller and transcutaneous energy transfer unit were placed. The AbioCor thoracic unit was placed in an orthotopic position after incision of the ventricals. There were 2 intraoperative deaths (due to intraoperative bleeding or aprotinin reaction). Four late deaths were recorded, 1 from multisystem organ failure and 3 cerebrovascular accidents. Autopsy revealed thrombus on the atrial struts of the 3 patients with cerebrovascular accident. Blood pumps and valves were clean on all patients. Significant morbidity was observed, primarily related to preexisting severity of illness. However, 3 patients recovered to the point of being able to take multiple trips outside of the hospital. Two patients were discharged from the hospital, with 1 patient being discharged home for more than 7 months. No significant device malfunctions or multi-system organ failure device-related infections were noted. The AbioCor IRH may be effective therapy for patients with end-stage heart failure. Many milestones have been achieved in the initial trial in humans, including the successful discharge of a patient to home and no significant device malfunctions. The occurrence of stroke is likely related to the presence of thrombus on the atrial struts and may be decreased as these atrial struts have been removed for future clinical implants.

Current status of the AbioCor implantable replacement heart

BACKGROUNDnThe AbioCor implantable replacement heart (IRH) has been developed as an alternative to transplant (ie, destination therapy). We report our experience with the AbioCor IRH in a bovine model at the University of Louisville.nnnMETHODSnMale Holstein cows were used (85 to 115 kg). The internal controller, battery, and secondary transcutaneous energy transfer coil were implanted in the right flank. After cardiopulmonary bypass, the thoracic unit was implanted orthotopically. After removal of air and weaning from cardiopulmonary bypass, the AbioCor was connected to internal components and energy transfer through transcutaneous energy transfer coils was achieved.nnnRESULTSnNineteen animals underwent implantation of the AbioCor IRH for a proposed 30-day duration. There were 6 deaths, none related to device malfunction. All animals demonstrated normal hemodynamics with normal pressures in the aorta, pulmonary artery, left atrium, and right atrium. There was no significant hemolysis and all animals demonstrated normal end organ function. The internal battery allowed for brief periods of untethered mobility.nnnCONCLUSIONSnThe AbioCor IRH has resulted in normal hemodynamics and normal end organ function without evidence of hemolysis in a bovine model.

The Total Artificial Heart: Where We Stand

The AbioCor® total artificial heart (TAH) is undergoing clinical feasibility testing as destination therapy in patients with end-stage congestive heart failure. So far, the device has been implanted in 11 of a projected 15 patients. The TAH has performed reliably, providing adequate circulatory support while extending survival and improving quality of life in most recipients. Thromboembolism remains a problem but is being addressed by optimizing device and patient management and refining the anticoagulation protocol. Because the device is totally implantable and requires no penetration of the skin, infection has been minimized. All recipients so far have been men. The device is large and this limits its use in smaller patients (i.e. women, small men and children). A smaller version is being developed. Although it has yet to receive Food and Drug Administration approval, the early clinical results suggest that the AbioCor TAH may become an accepted alternative to heart transplantation for selected patients with end-stage congestive heart failure. Further investigation with regard to its primary clinical applicability, i.e. as a rescue device for sudden catastrophic heart failure, is warranted.

A prospective comparison of alginate-hydrogel with standard medical therapy to determine impact on functional capacity and clinical outcomes in patients with advanced heart failure (AUGMENT-HF trial)

Aims AUGMENT-HF was an international, multi-centre, prospective, randomized, controlled trial to evaluate the benefits and safety of a novel method of left ventricular (LV) modification with alginate-hydrogel. Methods Alginate-hydrogel is an inert permanent implant that is directly injected into LV heart muscle and serves as a prosthetic scaffold to modify the shape and size of the dilated LV. Patients with advanced chronic heart failure (HF) were randomized (1 : 1) to alginate-hydrogel (n = 40) in combination with standard medical therapy or standard medical therapy alone (Control, n = 38). The primary endpoint of AUGMENT-HF was the change in peak VO2 from baseline to 6 months. Secondary endpoints included changes in 6-min walk test (6MWT) distance and New York Heart Association (NYHA) functional class, as well as assessments of procedural safety. Results Enrolled patients were 63 ± 10 years old, 74% in NYHA functional class III, had a LV ejection fraction of 26 ± 5% and a mean peak VO2 of 12.2 ± 1.8 mL/kg/min. Thirty-five patients were successfully treated with alginate-hydrogel injections through a limited left thoracotomy approach without device-related complications; the 30-day surgical mortality was 8.6% (3 deaths). Alginate-hydrogel treatment was associated with improved peak VO2 at 6 months—treatment effect vs. Control: +1.24 mL/kg/min (95% confidence interval 0.26–2.23, P = 0.014). Also 6MWT distance and NYHA functional class improved in alginate-hydrogel-treated patients vs. Control (both P < 0.001). Conclusion Alginate-hydrogel in addition to standard medical therapy for patients with advanced chronic HF was more effective than standard medical therapy alone for improving exercise capacity and symptoms. The results of AUGMENT-HF provide proof of concept for a pivotal trial. Trial Registration Number NCT01311791.

Results after partial left ventriculectomy versus heart transplantation for idiopathic cardiomyopathy

OBJECTIVEnPartial left ventriculectomy has been introduced as an alternative surgical therapy to heart transplantation. We performed a single-center, retrospective analysis of all patients with idiopathic dilated cardiomyopathy who underwent partial left ventriculectomy or heart transplantation or who were listed for transplantation to determine operative mortality rate, 12-month survival, freedom from death on the heart transplantation waiting list, and freedom from death or need for relisting for heart transplantation.nnnMETHODSnPatients who had partial left ventriculectomy (October 1996 to April 1998) were retrospectively compared with patients who were listed for heart transplantation (January 1995 to April 1998). Survival was assessed after the surgical procedure (partial left ventriculectomy vs heart transplantation) and from time of listing for heart transplantation to assess the additional impact of waiting list deaths. Freedom from death or relisting for heart transplantation was also compared.nnnRESULTSnThere was no difference in age or United Network for Organ Sharing status between the 2 groups. Twenty-nine patients with idiopathic dilated cardiomyopathy were listed for heart transplantation; 17 patients underwent transplantation, 6 patients died while on the waiting list, and 6 patients remain listed. One patient died after heart transplantation, and 1 patient required relisting. Sixteen patients had partial left ventriculectomy; 10 patients are in improved condition, 2 patients died (1 death early from sepsis and 1 death from progressive heart failure), and 4 patients required relisting for heart transplantation. Operative survival was 94% after partial left ventriculectomy and 94% after heart transplantation (P =.92). Postoperative 12-month Kaplan-Meier survival was 86% after partial left ventriculectomy and 93% after heart transplantation (P =.90). Twelve-month Kaplan-Meier survival after listing for heart transplantation was 75% due to death while on the waiting list (P =.76). Freedom from death or need for relisting for heart transplantation was 56% after partial left ventriculectomy and 86% after transplantation (P =.063).nnnCONCLUSIONnOperative and 12-month survival after partial left ventriculectomy and heart transplantation were comparable. However, despite their initial improvement, many patients who underwent partial left ventriculectomy required relisting for transplantation. Although partial left ventriculectomy is associated with acceptable operative and 12-month survival, it may prove to serve better as a bridge to transplantation in patients with idiopathic dilated cardiomyopathy rather than definitive therapy, given the number of patients who required relisting for transplantation.

One-year follow-up results from AUGMENT-HF: a multicentre randomized controlled clinical trial of the efficacy of left ventricular augmentation with Algisyl in the treatment of heart failure

AUGMENT‐HF was an international, multicentre, prospective, open‐label, randomized, controlled evaluation testing the hypothesis that Algisyl (injectable calcium alginate hydrogel) is superior to standard medical therapy (SMT) for improving functional capacity and clinical outcomes in patients with advanced heart failure (HF). We previously reported results following 6 months of follow‐up. This report presents the results from 1 year of extended follow up for this clinical trial.

Intraoperative Evaluation of the HeartMate II Flow Estimator

BACKGROUNDnDirect measurement of blood flow output has been incorporated into ventricular assist devices (VADs), but long-term reliability of the additional device components has raised concerns regarding sensor drift and failure. As an alternative approach, the HeartMate II axial VAD (Thoratec Corp, Pleasanton, CA) estimates device flow output from power consumption and rotational speed of the device motor. This study evaluated the accuracy of HeartMate II flow estimation at the time of implantation.nnnMETHODSnIn 20 patients, intraoperative blood flow measurement of the HeartMate II flow estimator was compared with flow values obtained with an ultrasonic flow probe placed around the device outflow graft. Estimated and measured VAD flow data were simultaneously recorded and digitally stored while the device motor speed varied from 7,800 to 11,000 rpm and while achieving device flow outputs of 2 to 7 liters/min. Estimated and measured flows were compared using linear regression analyses and root mean square error.nnnRESULTSnHeartMate II flow estimation (FE) demonstrated a linear correlation with ultrasonic flow probe (FP) measurements: FE = 0.74 FP + 0.99 (R(2) = 0.56, p = 0.0001). A root mean square error of 0.8 liters/min was observed between flow estimation and direct flow measurement and suggests a 15% to 20% difference at flows of 4 of 6 liters/min.nnnCONCLUSIONSnThese results suggest that HeartMate II flow estimation may be used to provide directional information for trend purposes rather than absolute values of device blood flow output. Patient management should include but not be limited to this information.

First human use of partial left ventricular heart support with the Circulite™ synergy™ micro-pump as a bridge to cardiac transplantation

In March 2007, a 46-year-old man without prior medical history suffered a large anterior myocardial infarction. Despite successful restoration of patency of the left anterior descending artery, he was left with an overall ejection fraction of 15%. He developed NYHA Class IV symptoms within 2xa0months and was accepted for heart transplantation. However, he continued to deteriorate over the ensuing 6 weeks and was re-admitted for treatment of dyspnea at rest.nnThe …