Faculty Bibliography

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.

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.

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.

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: Data from 3 institutions revealed an abrupt increase in HeartMate II (Thoratec) pump thrombosis starting in 2011, associated with 48% mortality at 6 months without transplantation or pump exchange. We sought to discover if the increase occurred nationwide in Interagency Registry for Mechanically Assisted Circulatory Support (INTERMACS) data, and if so (1) determine if accelerated risk continued, (2) identify predictors, (3) investigate institutional variability, and (4) assess mortality after pump thrombosis. METHODS: From April 2008 to June 2014, 11,123 HeartMate II devices were implanted at 146 institutions. Machine learning, non-parametric Random Forests for Survival was used to explore risk-adjusted thrombosis based on 87 pre-implant and implant variables, including implant date. RESULTS: A total of 995 pumps thrombosed, with risk peaking within weeks of implant. The risk-adjusted increase in pump thrombosis began in 2010, reached a maximum in 2012, and then plateaued at a level that was 3.3-times higher than pre-2010. Pump exchange, younger age, and larger body mass index were important predictors, and institutional variability was largely explained by implant date, patient profile, and duration of support. The probability of death within 3 months after pump thrombosis was 24%. CONCLUSIONS: Accelerated risk of HeartMate II thrombosis was confirmed by Interagency Registry for Mechanically Assisted Circulatory Support data, with risk subsequently leveling at a risk-adjusted rate higher than observed pre-2010. This elevated thrombosis risk emphasizes the need for improved mechanical circulatory support systems and post-market surveillance of adverse events. Clinicians cognizant of these new data should incorporate them into their and their patients' expectations and understanding of risks relative to those of transplantation and continued medical therapy.

Post-explant evaluation of the continuous-flow total artificial heart in preclinical studies can be extremely challenging because of the device's unique architecture. Determining the exact location of tissue regeneration, neointima formation, and thrombus is particularly important. In this report, we describe our first successful experience with visualizing the Cleveland Clinic continuous-flow total artificial heart using a custom-made high-definition miniature camera.