Faculty Bibliography

Appropriate early anticoagulation after left ventricular assist device (LVAD) implantation has not been established with practices ranging from no anticoagulation to early heparinization. The goal of this study was to evaluate the efficacy and morbidity of three strategies before initiating oral anticoagulation therapy. This was a noninterventional, retrospective, matched historical control cohort study. The primary and secondary endpoints were thrombotic complications (TCs) and bleeding up to 30 days post-LVAD implantation. There was a significant difference in the overall rate of TCs between strategies (p = 0.017). The incidence of TCs was significantly lower in the heparin group versus no bridging (4.9 vs. 27.0%, p = 0.008) on univariate analysis. On multivariate analysis, heparin was independently associated with a lower odds of TCs (odds ratio [OR], 0.10; 95% confidence interval [CI], 0.01-0.85). No differences were observed in bleeding between groups (p = 0.127) on univariate analysis; however, heparin was independently associated with increased odds of bleeding compared with no bridging on multivariate analysis (OR, 2.93; 95% CI, 1.15-7.43). Compared with no bridging, bivalirudin did not significantly differ in TC or bleeding events. Heparin seems to be the most effective regimen to use post-LVAD implantation but may increase the patient's risk for bleeding.

There is insufficient data on patients with small body size to determine if this should be considered a risk factor for continuous-flow left ventricular assist device (CF-LVAD) support. We sought to evaluate survival outcomes, adverse events, and functional status of CF-LVAD patients with body surface area (BSA) <1.5 m in a large national registry. Adults with BSA < 1.5 m (n = 128) implanted with a HeartMate II (HMII)-LVAD from the Interagency Registry for Mechanically Assisted Circulatory Support registry from April 2008 to December 2012 formed this cohort. Outcomes were compared with HMII bridge to transplant (BTT) and destination therapy (DT) post approval studies. The majority of patients were female (n = 106, 83%). A total of 64% (n = 82) were implanted for BTT and 36% (n = 46) for DT. The median BSA (range) was 1.44 (1.19-1.49) and 1.45 (1.25-1.49) m for BTT and DT, respectively. Overall survival 1 year post implant was 81% +/- 5% for BTT and 84% +/- 6% for DT. The most common adverse events for BTT and DT patients were bleeding (0.91, 0.88 events/patient year) and driveline infection (16%, 0.28 events/patient year). Six months post implantation, 87% of BTT and 77% of DT patients were New York Heart Association functional class I or II. Post implant survival, functional status improvement, and adverse event profile for adult BTT and DT HMII patients with BSA < 1.5 m are favorable and comparable with outcomes published in the overall patient population.

The Cleveland Clinic continuous-flow total artificial heart passively regulates itself in regard to the relative performance of systemic and pulmonary pumps. The system incorporates real-time monitoring to detect any indication of incipient left or right suction as input for automatic controller response. To recognize suction, the external controller compares the waveforms of modulating speed input and power feedback. Deviations in periodic waveforms indicate sudden changes to flow impedance, which are characteristic of suction events as the pump speed is modulating. Incipient suction is indicated within 3 seconds of being detected in the power wave form, allowing timely controller response before mean flow is affected. This article describes the results obtained from subjecting the system to severe hemodynamic manipulation during an acute study in a calf.

BACKGROUND: Left ventricular assist device (LVAD) infections including drivelines, pump pockets, and bacteremia are difficult to manage and conservative treatments may not be effective as the infected foreign material remains. METHODS: We performed a retrospective analysis of all 170 HeartMate II (Thoratec, Pleasanton, CA) implantations as bridge to transplant (BTT) between 2004 and 2012 at our institution. Sixty-one patients (36%) developed a culture positive driveline infection, pump pocket infection, bacteremia, or a combination of these. Twenty-six out of 61 patients with an infection and 49 out of 109 patients without an infection went on to receive a heart transplant. RESULTS: The 1- and 3-year freedom from LVAD infection was 60% and 32%, respectively. While early infection tends to first present as driveline infections, late infections tend to present initially as bacteremia. The 1-year likelihood of receiving a transplant in the patients with an LVAD infection group was 37%, compared with 43% in patients without an infection (p = 0.36). One-year survival to transplantation was 76% in patients with LVAD infection compared with 81% without (p = 0.33). The 1- and 3-year posttransplant survival in patients with a LVAD infection was 96% and 91%, respectively, compared with 92% and 88% in patients without an infection (p = 0.48) . CONCLUSIONS: In this nonmatched cohort of LVAD patients with and without infection, selected patients with controlled LVAD infection have an equal chance of getting transplanted with excellent early and late post-transplant survival.

OBJECTIVE: The Cleveland Clinic continuous-flow total artificial heart (CFTAH) is a compact, single-piece, valveless, pulsatile pump providing self-regulated hemodynamic output to left/right circulation. We evaluated chronic in vivo pump performance, physiologic and hemodynamic parameters, and biocompatibility of the CFTAH in a well-established calf model. METHODS: CFTAH pumps have been implanted in 17 calves total. Hemodynamic parameters, pump performance, and device-related adverse events were evaluated during studies and at necropsy. RESULTS: In vivo experiments demonstrated good hemodynamic performance (pump flow, 7.3 +/- 0.7 L/min; left atrial pressure, 16 +/- 3 mm Hg; right atrial pressure, 17 +/- 3 mm Hg; right atrial pressure-left atrial pressure difference, 1 +/- 2 mm Hg; mean arterial pressure, 103 +/- 7 mm Hg; arterial pulse pressure, 30 +/- 11 mm Hg; and pulmonary arterial pressure, 34 +/- 5 mm Hg). The CFTAH has operated within design specifications and never failed. With ever-improving pump design, the implants have shown no chronic hemolysis. Three animals with recent CFTAH implantation recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last 2 were intended to be 90-day studies). All these longest-surviving cases showed good biocompatibility, with no thromboembolism in organs. CONCLUSIONS: The current CFTAH has demonstrated reliable self-regulation of hemodynamic output and acceptable biocompatibility without anticoagulation throughout 90 days of chronic implantation in calves. Meeting these milestones is in accord with our strategy to achieve transfer of this unique technology to human surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy.

In vivo preclinical testing of mechanical circulatory devices requires large animal models that provide reliable physiological and hemodynamic conditions by which to test the device and investigate design and development strategies. Large bovine species are commonly used for mechanical circulatory support device research. The animals used for chronic in vivo support require high-quality care and excellent surgical techniques as well as advanced methods of postoperative care. These techniques are constantly being updated and new methods are emerging.We report results of our double steel-wire closure technique in large bovine models used for Cleveland Clinic's continuous-flow total artificial heart development program. This is the first report of double-wire sternal fixation used in large bovine models.

Despite significant improved survival with continuous flow left ventricular assist devices (LVADs), complications related to aortic valve insufficiency, gastrointestinal bleeding, stroke, pump thrombosis, and hemolysis have dampened the long term success of these pumps. Evolution has favored a pulsatile heart pump to be able to deliver the maximum flow at different levels of systemic vascular resistance, confer kinetic energy to the flow of blood past areas of stenosis and generate low shear stress on blood elements. In this perspective, we suggest that lack of pulsatility may be one factor that has limited the success of continuous flow LVADs and suggest that research needs to focus on methods to generate pulsatility either by the native heart or by various speed modulation algorithms.

Implantation of mechanical circulatory support devices is challenging, especially in patients with a small chest cavity. We evaluated how well the Cleveland Clinic continuous-flow total artificial heart (CFTAH) fit the anatomy of patients about to receive a heart transplant. A mock pump model of the CFTAH was rapid-prototyped using biocompatible materials. The model was brought to the operative table, and the direction, length, and angulation of the inflow/outflow ports and outflow conduits were evaluated after the recipient's ventricles had been resected. Thoracic cavity measurements were based on preoperative computed tomographic data. The CFTAH fit well in all five patients (height, 170 +/- 9 cm; weight, 75 +/- 24 kg). Body surface area was 1.9 +/- 0.3 m (range, 1.6-2.1 m). The required inflow and outflow port orientation of both the left and right housings appeared consistent with the current version of the CFTAH implanted in calves. The left outflow conduit remained straight, but the right outflow direction necessitated a 73 +/- 22 degree angulation to prevent potential kinking when crossing over the connected left outflow. These data support the fact that our design achieves the proper anatomical relationship of the CFTAH to a patient's native vessels.