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. Hemodynamics, 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 [LAP], 16 ± 3 mm Hg; right atrial pressure [RAP], 17 ± 3 mm Hg; RAP-LAP difference, 1 ± 2 mm Hg; mean arterial pressure, 103 ± 7 mm Hg; arterial pulse pressure, 30 ± 11 mm Hg; 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 recent animals with the CFTAH recovered well, with no postoperative anticoagulation, during planned in vivo durations of 30, 90, and 90 days (last two 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 surgical practice, thus filling the urgent need for cardiac replacement devices as destination therapy.
Background
Glucose-insulin-potassium (GIK) administration during cardiac surgery
inconsistently improves myocardial function, perhaps because hyperglycemia
negates the beneficial effects of GIK. The hyperinsulinemic normoglycemic
clamp (HNC) technique may better enhance the myocardial benefits of GIK. We
extended previous GIK investigations by: 1) targeting normoglycemia while
administering a glucose-insulin-potassium infusion (HNC); 2) using improved
echocardiographic measures of myocardial deformation, specifically
myocardial longitudinal strain and strain rate; and, 3) assessing activation
of glucose metabolic pathways.
Methods
100 patients having aortic valve replacement for aortic stenosis were
randomly assigned to HNC (high-dose insulin with concomitant glucose
infusion titrated to normoglycemia) versus standard therapy (insulin
treatment if glucose >150 mg/dL). Our primary outcomes were left
ventricular longitudinal strain and strain rate, assessed using
speckle-tracking echocardiography. Right atrial tissue was analyzed for
activation of glycolysis/pyruvate oxidation and alternative metabolic
pathways.
Results
Time-weighted mean glucose concentrations were lower with HNC
(127±19 mg/dL) than standard care (177±41 mg/dL;
P<0.001). Echocardiographic data were adequate in 72
patients for strain analysis and 67 patients for strain rate analysis. HNC
did not improve myocardial strain, with an HNC minus standard therapy
difference of −1.2 (97.5%CI: −2.9, 0.5)%;
P=0.11. Strain rate was significantly better,
but by a clinically unimportant amount: −0.16 (−0.30,
−0.03) sec−1, P = 0.007.
There was no evidence of increased glycolytic, pyruvate oxidation, or
hexosamine biosynthetic pathway activation in right atrial samples (n
= 20, HNC; 22, standard therapy).
Conclusions
Administration of glucose and insulin while targeting normoglycemia
during aortic valve replacement did not meaningfully improve myocardial
function.
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