New continuous-flow total artificial heart and vascular permeability.

BACKGROUND: We tested the short-term effects of completely nonpulsatile versus pulsatile circulation after ventricular excision and replacement with total implantable pumps in an animal model on peripheral vascular permeability. METHODS: Ten calves underwent cardiac replacement with two HeartMate III continuous-flow rotary pumps. In five calves, the pump speed was rapidly modulated to impart a low-frequency pulse pressure in the physiologic range (10-25 mm Hg) at a rate of 40 pulses per minute (PP). The remaining five calves were supported with a pulseless systemic circulation and no modulation of pump speed (NP). Skeletal muscle biopsies were obtained before cardiac replacement (baseline) and on postoperative days (PODs) 1, 7, and 14. Skeletal muscle-tissue water content was measured, and morphologic alterations of skeletal muscle were assessed. VE-cadherin, phospho-VE-cadherin, and CD31 were analyzed by immunohistochemistry. RESULTS: There were no significant changes in tissue water content and skeletal muscle morphology within group or between groups at baseline, PODs 1, 7, and 14, respectively. There were no significant alterations in the expression and/or distribution of VE-cadherin, phospho-VE-cadherin, and CD31 in skeletal muscle vasculature at baseline, PODs 1, 7, and 14 within each group or between the two groups, respectively. Although continuous-flow total artificial heart (CFTAH) with or without a pulse pressure caused slight increase in tissue water content and histologic damage scores at PODs 7 and 14, it failed to reach statistical significance. CONCLUSIONS: There was no significant adherens-junction protein degradation and phosphorylation in calf skeletal muscle microvasculature after CFTAH implantation, suggesting that short term of CFTAH with or without pulse pressure did not cause peripheral endothelial injury and did not increase the peripheral microvascular permeability.

Continuous-flow ventricular assist device exchange is safe and effective in prolonging support time in patients with end-stage heart failure.

OBJECTIVE: Although the development of continuous-flow ventricular assist devices (CF-VAD) has improved the reliability of these devices, VAD exchange is still occasionally necessary. The focus of this study was to analyze our institution's entire experience with primary CF-VAD implants, evaluate the baseline variables, determine which factors predict the need for exchange, and evaluate the impact of exchange on survival and event-free survival. METHODS: We retrospectively reviewed the data of all patients in a single center who received a primary CF-VAD implant between December 1999 and December 2013. All CF-VAD exchanges were reviewed; demographics, indications, preoperative and operative data, and clinical outcomes were summarized. Univariate and multivariable regression analyses were performed to ascertain predictors for exchange. Time-to-event and survival analyses were also performed. RESULTS: We identified 469 patients who underwent 546 CF-VAD implantations. Of these patients, 66 (14%) underwent 77 exchanges from one CF-VAD to another. The primary indications included hemolysis or thrombosis (n = 49; 63.6%), infection (n = 9; 11.7%), or other causes (n = 19; 24.7%). Survival was not significantly different between the exchange and nonexchange groups. Multivariable regression analysis identified a history of cerebrovascular events as a significant predictor for exchange. Among exchange patients, 11 underwent heart transplantation, 3 had their CF-VADs explanted, 26 had ongoing support, and 26 died during device support. CONCLUSIONS: In our series of contemporary CF-VAD exchanges, a history of previous cerebrovascular events was a significant predictor for exchange. Exchange did not affect early or late survival. Our data suggest that aggressive surgical treatment of pump-related complications with exchange is safe and justified.

Ninety-day survival of a calf implanted with a continuous-flow total artificial heart.

We evaluated the effects of steady state flow and perfusion on end-organ function in a long-term calf model. The animal received a continuous-flow total artificial heart (CFTAH) that we created from two axial-flow ventricular assist devices. Pump flow, blood pressure, and other pump parameters were monitored throughout the study, as were arterial blood gas and hematologic values, including neurohormone levels. Some hematologic values were mildly abnormal transiently after surgery but returned to acceptable levels within the first week. During the 90-day study, the calf showed no signs of hemolysis or thrombosis. Its mental function remained normal, as evidenced by the animal's interest in its surroundings and response to stimuli. End-organ and vasomotor function was not adversely affected by 90 days of steady state flow. This was the first study in which CFTAH support of an animal model was maintained for this duration.

Eight-year experience with a continuous-flow total artificial heart in calves.

Over the last 8 years, we have developed and evaluated a continuous-flow total artificial heart (CFTAH) comprising two rotary blood pumps. To understand the physiologic effects of nonpulsatile circulation, we evaluated the CFTAH in 65 calves for 90 days or less. We describe our experience with 29 calves that survived for 7 days or more. The calves received dual axial-flow (n = 24) or centrifugal-flow (n = 5) pumps. Several iterations of customized atrial cuffs were developed to facilitate an adequate anatomical fit. Pressures (arterial pressure [AoP], pulmonary artery pressure [PAP], left atrial pressure [LAP], and right atrial pressure [RAP]) and pump parameters were continuously monitored. Hematologic and biochemistry values were analyzed. After each case, a necropsy was performed. The calves survived for 7-92 days (mean, 24 days). Pressures were 94 ± 14 (AoP), 25 ± 8 (PAP), 14 ± 6 (RAP), and 16 ± 6 (LAP) mm Hg. Pump flow was maintained at 9.1 ± 1.7 L/minute (right) and 9.4 ± 1.9 L/minute (left). Hematologic and biochemistry values remained acceptable. Eight animals underwent treadmill evaluations, in which oxygen consumption (VO2) was comparable with physiologic total-body VO2. In the two animals that survived to 90 days, the end-organs appeared unremarkable at autopsy, and the CFTAH circuits were free of thrombus. Our results show that a CFTAH can maintain a large animal physiologically and hemodynamically for up to 90 days with continuous flow.

Anatomic fitting of total artificial hearts for in vivo evaluation.

Successful anatomic fitting of a total artificial heart (TAH) is vital to achieve optimal pump hemodynamics after device implantation. Although many anatomic fitting studies have been completed in humans prior to clinical trials, few reports exist that detail the experience in animals for in vivo device evaluation. Optimal hemodynamics are crucial throughout the in vivo phase to direct design iterations and ultimately validate device performance prior to pivotal human trials. In vivo evaluation in a sheep model allows a realistically sized representation of a smaller patient, for which smaller third-generation TAHs have the potential to treat. Our study aimed to assess the anatomic fit of a single device rotary TAH in sheep prior to animal trials and to use the data to develop a three-dimensional, computer-aided design (CAD)-operated anatomic fitting tool for future TAH development. Following excision of the native ventricles above the atrio-ventricular groove, a prototype TAH was inserted within the chest cavity of six sheep (28-40 kg). Adjustable rods representing inlet and outlet conduits were oriented toward the center of each atrial chamber and the great vessels, with conduit lengths and angles recorded for future analysis. A three-dimensional, CAD-operated anatomic fitting tool was then developed, based on the results of this study, and used to determine the inflow and outflow conduit orientation of the TAH. The mean diameters of the sheep left atrium, right atrium, aorta, and pulmonary artery were 39, 33, 12, and 11 mm, respectively. The center-to-center distance and outer-edge-to-outer-edge distance between the atria, found to be 39 ± 9 mm and 72 ± 17 mm in this study, were identified as the most critical geometries for successful TAH connection. This geometric constraint restricts the maximum separation allowable between left and right inlet ports of a TAH to ensure successful alignment within the available atrial circumference.