Faculty Bibliography

With the advances of mechanical circulatory support, the selection of patients has undergone many changes over the last decade. Determining who is suitable for left ventricular assist device (LVAD) implantation is important to understanding the overall risk and outcomes. As devices improve, it is expected that changes will continue in this field. This review describes current state of patient selection, evaluation, and optimization prior to implantation of a long-term circulatory support device.

BACKGROUND: We observed an apparent increase in the rate of device thrombosis among patients who received the HeartMate II left ventricular assist device, as compared with preapproval clinical-trial results and initial experience. We investigated the occurrence of pump thrombosis and elevated lactate dehydrogenase (LDH) levels, LDH levels presaging thrombosis (and associated hemolysis), and outcomes of different management strategies in a multi-institutional study. METHODS: We obtained data from 837 patients at three institutions, where 895 devices were implanted from 2004 through mid-2013; the mean (+/-SD) age of the patients was 55+/-14 years. The primary end point was confirmed pump thrombosis. Secondary end points were confirmed and suspected thrombosis, longitudinal LDH levels, and outcomes after pump thrombosis. RESULTS: A total of 72 pump thromboses were confirmed in 66 patients; an additional 36 thromboses in unique devices were suspected. Starting in approximately March 2011, the occurrence of confirmed pump thrombosis at 3 months after implantation increased from 2.2% (95% confidence interval [CI], 1.5 to 3.4) to 8.4% (95% CI, 5.0 to 13.9) by January 1, 2013. Before March 1, 2011, the median time from implantation to thrombosis was 18.6 months (95% CI, 0.5 to 52.7), and from March 2011 onward, it was 2.7 months (95% CI, 0.0 to 18.6). The occurrence of elevated LDH levels within 3 months after implantation mirrored that of thrombosis. Thrombosis was presaged by LDH levels that more than doubled, from 540 IU per liter to 1490 IU per liter, within the weeks before diagnosis. Thrombosis was managed by heart transplantation in 11 patients (1 patient died 31 days after transplantation) and by pump replacement in 21, with mortality equivalent to that among patients without thrombosis; among 40 thromboses in 40 patients who did not undergo transplantation or pump replacement, actuarial mortality was 48.2% (95% CI, 31.6 to 65.2) in the ensuing 6 months after pump thrombosis. CONCLUSIONS: The rate of pump thrombosis related to the use of the HeartMate II has been increasing at our centers and is associated with substantial morbidity and mortality.

BACKGROUND: The HeartWare left ventricular assist device (HVAD, HeartWare Inc, Framingham, MA) is the first implantable centrifugal continuous-flow pump approved for use as a bridge to transplantation. An infrequent but serious adverse event of LVAD support is thrombus ingestion or formation in the pump. In this study, we analyze the incidence of pump thrombus, evaluate the comparative effectiveness of various treatment strategies, and examine factors pre-disposing to the development of pump thrombus. METHODS: The analysis included 382 patients who underwent implantation of the HVAD as part of the HeartWare Bridge to Transplant (BTT) and subsequent Continued Access Protocol (CAP) trial. Descriptive statistics and group comparisons were generated to analyze baseline characteristics, incidence of pump thrombus, and treatment outcomes. A multivariate analysis was performed to assess significant risk factors for developing pump thrombus. RESULTS: There were 34 pump thrombus events observed in 31 patients (8.1% of the cohort) for a rate of 0.08 events per patient-year. The incidence of pump thrombus did not differ between BTT and CAP. Medical management of pump thrombus was attempted in 30 cases, and was successful in 15 (50%). A total of 16 patients underwent pump exchange, and 2 underwent urgent transplantation. Five patients with a pump thrombus died after medical therapy failed, 4 of whom also underwent a pump exchange. Survival at 1 year in patients with and without a pump thrombus was 69.4% and 85.5%, respectively (p = 0.21). A multivariable analysis revealed that significant risk factors for pump thrombus included a mean arterial pressure > 90 mm Hg, aspirin dose /= 3 at implant. CONCLUSIONS: Pump thrombus is a clinically important adverse event in patients receiving an HVAD, occurring at a rate of 0.08 events per patient-year. Significant risk factors for pump thrombosis include elevated blood pressure and sub-optimal anti-coagulation and anti-platelet therapies. This suggests that pump thrombus event rates could be reduced through careful adherence to patient management guidelines.

BACKGROUND: The incidence of percutaneous lead failure among patients supported with a HeartMate II left ventricular assist device is unknown. METHODS: All HeartMate II left ventricular assist device driveline dysfunctions reported to Thoratec Corporation were retrospectively reviewed. The location and severity of driveline failures and their association with adverse clinical outcomes were examined. Also, the effect of design modifications was evaluated. RESULTS: Between 2004 and October 2012, 12,969 HeartMate II pumps were implanted worldwide. The incidence of percutaneous lead dysfunction was 1,418 events occurring in 1,198 pumps (9.2% of pumps) over a cumulative support period of 13,932 patient-years (maximum, 8 years). Lead failure was mostly in the externalized part of the cable (87.2%). Lead dysfunction was managed by clamshell reinforcement of the external connector strain relief or by tape or silicone cable reinforcement in 76% of cases. Mortality or significant morbidity, including pump exchange or urgent transplant, or more complex cable repair occurred in 2.3% of all implanted pumps. The cumulative incidence of lead failures leading to major adverse clinical events has decreased with two lead design revisions: at 18 months postimplantation, the incidence was 6.2%+/-1.2% for the original design versus 2.2%+/-0.5% for the latest design change introduced in 2010 (log-rank p<0.001). CONCLUSIONS: Lead failures remain an important factor in the durability of left ventricular assist devices during long-term support. Most lead failures in the HeartMate II occurred in the externalized portion of the driveline, suggesting lead fatigue. The incidence of both internal and external lead failures has diminished since 2004 with improvements in lead design.

Heart failure remains one of the most prevalent diseases worldwide and in recent decades, left ventricular assist devices (LVADs) have become an important treatment option. With increasing device experience, there is particular interest in the use of LVADs as a bridge to recovery that allows the patient's heart to undergo reverse remodeling, whereby the device can be explanted and the heart can function at an improved state. There are many considerations that play a role in this process, including the ability of the device to unload the heart, the innate physiology of the heart to recover and the use of concomitant therapies. This review provides an overview of the most current literature as it pertains to these processes and gives a view into the future directions of LVADs as a tool for achieving myocardial recovery.

OBJECTIVES: We designed a device that applies motion-activated energy (vibration) to prevent chest-tube clogging and maintain tube patency. We evaluated the efficacy of this device in vitro and in vivo. METHODS: The motion-activated system (MAS) device assembly comprises a direct current motor with an eccentric mass (3.2 g, centroid radius of 4.53 mm) affixed to its motor shaft. The device was tested in vitro using a model of an obstructed chest tube, with clots of bovine blood and human thrombin. The in vivo study (in nine healthy pigs, 46.0 +/- 3.3 kg) involved a bilateral minithoracotomy and placement of 32-Fr chest tubes (with and without the device). Whole autologous blood (120 ml) was injected every 15 min into the right and left chest each over 120 min total. RESULTS: Chest-tube drainage over these 2 h using the MAS was significantly higher than that without the device (369 +/- 113 ml vs 209 +/- 115 ml; P = 0.027). CONCLUSIONS: Our results suggest that the motion-activation of the chest tubes may be an effective tool to maintain chest tubes patent. Further optimization of this technology is required to obtain more consistent prevention of clot deposition within or outside the chest tubes.

BACKGROUND: The DuraHeart is a continuous centrifugal-flow left ventricular assist device that uses active magnetic levitation for impeller positioning designed for improved hemocompatibility and durability. This study reviews the results of the US trial with specific attention to hemolysis, thrombotic complications, and pump failure. METHODS: The US SUSTAIN trial was a multicenter, prospective, single-arm observational study in advanced heart failure patients listed for transplantation. Follow-up was complete in 100% of the patients at 6 months. RESULTS: Sixty-three patients were enrolled at 23 centers. Forty-six patients (73%) reached the primary end points of survival to transplantation, alive on the original device at 180 days and listed for transplantation, or explant for recovery. Median duration of support was 267 days (range, 10 to 952 days) with a total support time of 46 patient-years. There was no clinical hemolysis reported during the study. Mean lactate dehydrogenase values peaked at day 4 and significantly decreased during support (435+/-236 U/L and 297+/-142 U/L on day 3 and day 180, respectively). There were no cases of pump thrombosis reported, and 3 cases of pump thrombus "in transit" (0.06 events/patient-year) were observed. There were 6 (10%) cases of magnetic levitation system failure, all secondary to cable wire fractures (0.12 events/patient-year). All patients were hemodynamically stable with the backup hydrodynamic mode. Major adverse events included gastrointestinal bleeding (0.52 events/patient-year), ischemic and hemorrhagic strokes (0.17 events/patient-year and 0.09 events/patient-year, respectively), and driveline infections (0.67 events/patient-year). CONCLUSIONS: The DuraHeart demonstrated good hemocompatibility; however, the reliability of full magnetic levitation systems should be a high priority in future pump designs.