Faculty Bibliography

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: Data for left ventricular assist devices (LVADs) in patients with noninotrope-dependent heart failure (HF) are limited. OBJECTIVES: The goal of this study was to evaluate HeartMate II (HMII) LVAD support versus optimal medical management (OMM) in ambulatory New York Heart Association functional class IIIB/IV patients meeting indications for LVAD destination therapy but not dependent on intravenous inotropic support. METHODS: This was a prospective, multicenter (N = 41), observational study of 200 patients (97 LVAD, 103 OMM). Entry criteria included >/=1 hospitalization for HF in the last 12 months and 6-min walk distance (6MWD) <300 m. The primary composite endpoint was survival on original therapy with improvement in 6MWD >/=75 m at 12 months. RESULTS: LVAD patients were more severely ill, with more patients classified as Interagency Registry for Mechanically Assisted Circulatory Support profile 4 (65% LVAD vs. 34% OMM; p < 0.001) than 5 to 7. More LVAD patients met the primary endpoint (39% LVAD vs. 21% OMM; odds ratio: 2.4 [95% confidence interval: 1.2 to 4.8]; p = 0.012). On the basis of as-treated analysis, 12-month survival was greater for LVAD versus OMM (80 +/- 4% vs. 63 +/- 5%; p = 0.022) patients. Adverse events were higher in LVAD patients, at 1.89 events/patient-year (EPPY), primarily driven by bleeding (1.22 EPPY), than with OMM, at 0.83 EPPY, primarily driven by worsening HF (0.68 EPPY). Most patients (80% LVAD vs. 62% OMM; p < 0.001) required hospitalizations. Health-related quality of life (HRQol) and depression improved from baseline more significantly with LVADs than with OMM (Delta visual analog scale: 29 +/- 25 vs. 10 +/- 22 [p < 0.001]; Delta Patient Health Questionnaire-9: -5 +/- 7 vs. -1 +/- 5 [p < 0.001]). CONCLUSIONS: Survival with improved functional status was better with HMII LVAD compared with OMM. Despite experiencing more frequent adverse events, LVAD patients improved more in HRQol and depression. The results support HMII use in functionally limited, noninotrope-dependent HF patients with poor HRQoL. (Risk Assessment and Comparative Effectiveness of Left Ventricular Assist Device [LVAD] and Medical Management [ROADMAP]; NCT01452802).

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.

OBJECTIVES: Pump-off testing to assess left ventricular recovery is not an option for continuous-flow left ventricular assist devices unless measures are taken to prevent pump regurgitation. The purpose of this bench study was to characterize the hemodynamics and pump flow of the HeartMate II (Thoratec Corp, Pleasanton, Calif) left ventricular assist device at 6000 rpm, the speed commonly used clinically to determine left ventricular recovery. METHODS: The HeartMate II device was operated in a mock loop at 3 speeds (6000, 8000, and 10,000 rpm). We acquired pressure-flow curves in each steady state. In pulsatile mode with the pneumatic ventricle (heart simulator) activated, pump flow, total flow, and aortic pressure data were obtained under conditions simulating normal heart function or heart failure. RESULTS: A large regurgitant flow during diastole was confirmed in normal heart function at 6000 rpm support; however, the net flow was zero, and there were no differences in the mean aortic pressure between 6000 rpm support and no left ventricular assist device support. In contrast, in the heart failure condition, left ventricular assist device flow at 6000 rpm significantly contributed to the mean aortic pressure and total flow because there was less regurgitant flow. CONCLUSIONS: The net pump flow generated by the HeartMate II device at 6000 rpm depends on the degree of residual left ventricular function. In the setting of improved left ventricular function, at 6000 rpm, we noted a large regurgitant flow that reloaded the left ventricle. Although this "marker" can serve as a useful indicator for left ventricular recovery, assessing left ventricular recovery at this speed is flawed unless measures are taken to prevent regurgitant flow.

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.

BACKGROUND: Anticoagulation with warfarin is common in patients presenting for heart transplant. Prior to surgery, anticoagulation reversal is necessary to avoid significant intraoperative and perioperative bleeding complications. Commonly, warfarin reversal is achieved with vitamin K and fresh frozen plasma (FFP); however, these therapies have significant limitations. An alternative to FFP for reversal exists with prothrombin complex concentrate (PCC). A warfarin reversal protocol prior to heart transplant was implemented using low-dose PCC at our institution. OBJECTIVE: To assess blood product use, effectiveness, and safety post-low-dose PCC administration in patients needing warfarin reversal prior to heart transplant compared with historical controls. METHODS: This was a single-center, retrospective cohort study. The PCC cohort included patients undergoing heart transplant presenting with an international normalized ratio >/=1.5 on warfarin therapy and who received at least 1 dose of PCC. Blood product use was measured from postoperative day 0 to 2. RESULTS: The PCC and historical control cohorts included 16 and 50 patients, respectively. There was a significant reduction in the use of FFP (4 vs 8 units, P = 0.0239) in the PCC cohort compared with the historical control cohort. No differences were identified in the use of other blood products as well as other secondary efficacy or safety end points. CONCLUSIONS: Use of PCC, per the reversal protocol, prior to heart transplant reduced FFP use and showed a non-statistically significant trend toward reductions in the use of other blood products in the intraoperative and perioperative setting, with no difference identified in thrombotic or embolic complications compared with historical controls.

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.