First clinical use of a bioprosthetic total artificial heart: report of two cases.

BACKGROUND: The development of artificial hearts in patients with end-stage heart disease have been confronted with the major issues of thromboembolism or haemorrhage. Since valvular bioprostheses are associated with a low incidence of these complications, we decided to use bioprosthetic materials in the construction of a novel artificial heart (C-TAH). We report here the device characteristics and its first clinical applications in two patients with end-stage dilated cardiomyopathy. The aim of the study was to evaluate safety and feasibility of the CARMAT TAH for patients at imminent risk of death from biventricular heart failure and not eligible for transplant. METHODS: The C-TAH is an implantable electro-hydraulically actuated pulsatile biventricular pump. All components, batteries excepted, are embodied in a single device positioned in the pericardial sac after excision of the native ventricles. We selected patients admitted to hospital who were at imminent risk of death, having irreversible biventricular failure, and not eligible for heart transplantation, from three cardiac surgery centres in France. FINDINGS: The C-TAH was implanted in two male patients. Patient 1, aged 76 years, had the C-TAH implantation on Dec 18, 2013; patient 2, aged 68 years, had the implantation on Aug 5, 2014. The cardiopulmonary bypass times for C-TAH implantation were 170 min for patient 1 and 157 min for patient 2. Both patients were extubated within the first 12 postoperative hours and had a rapid recovery of their respiratory and circulatory functions as well as a normal mental status. Patient 1 presented with a tamponade on day 23 requiring re-intervention. Postoperative bleeding disorders prompted anticoagulant discontinuation. The C-TAH functioned well with a cardiac output of 4·8-5·8 L/min. On day 74, the patient died due to a device failure. Autopsy did not detect any relevant thrombus formation within the bioprosthesis nor the different organs, despite a 50-day anticoagulant-free period. Patient 2 experienced a transient period of renal failure and a pericardial effusion requiring drainage, but otherwise uneventful postoperative course. He was discharged from the hospital on day 150 after surgery with a wearable system without technical assistance. After 4 months at home, the patient suffered low cardiac output. A change of C-TAH was attempted but the patient died of multiorgan failure. INTERPRETATION: This preliminary experience could represent an important contribution to the development of total artificial hearts using bioprosthetic materials. FUNDING: CARMAT SA.

Comparison of the inflammatory response between miniaturized and standard CPB circuits in aortic valve surgery.

OBJECTIVE: One of the complications of CPB is the systemic inflammatory response syndrome (SIRS). Recent developments tend to minimize the biological impact of CPB in using miniaturized closed circuit with reduced priming volume and less blood-air interface. The benefit of these miniaturized closed circuits in terms of inflammatory response has been proved in coronary surgery. However, in open heart surgery, the CPB circuit is no more closed and the benefit of the miniaturized set-up could disappear. The aim of the study is to compare the SIRS between standard and miniaturized circuits in aortic surgery. METHODS: Forty patients who underwent singular aortic valve replacement were randomly assigned either to a standard CPB (group A, n=20) or to a miniaturized CPB (group B, n=20). Pertinent clinical and surgical data were collected. Hematological parameters (leukocyte and neutrophil counts) and biochemical parameters (C-reactive protein, cytokine tests) were determined pre-, on and post-CPB. RESULTS: There were an increase in leukocyte and neutrophil counts and a decline in hematocrit in both groups. In both groups, there was a raise after CPB, in C-reactive protein, IL-6, TNF-alpha, neutrophil elastase, and IL-10. However, the raises of elastase and TNF-alpha were significantly lower after the weaning of miniaturized CPB (116+/-46 ng/ml and 10+/-4 pg/ml, respectively) compared to standard CPB (265+/-120 ng/ml, P=0.01 and 18+/-7 pg/ml, P=0.03). The raise of IL-10 is also lower with miniaturized circuit (15+/-6 pg/ml) compared to standard circuit (51+/-26, P=0.004). CONCLUSIONS: This study demonstrates in aortic surgery, the lesser inflammatory response of a miniaturized CPB compared to a standard CPB. However, there is always some inflammation after CPB and a small bio-reactive free perfusion circuit is still to be found in open heart surgery.

Reduction of the inflammatory response following coronary bypass grafting with total minimal extracorporeal circulation.

OBJECTIVE: Cardiopulmonary bypass (CPB) is known to cause part of the systemic inflammatory reaction after cardiac surgery that can be responsible for organ failure. A novel technique based on a minimal extracorporeal circulation (MECC(R)) system has been evaluated with regard to the inflammatory response in a prospective study involving patients undergoing coronary artery bypass grafting. METHODS: Sixty consecutive patients were randomly assigned to either standard normothermic CPB (n=30) or the MECC system, with a reduced priming volume, no aortic venting and no venous reservoir, excluding the blood-air interface (n=30). Specific evaluation of cytokine release (IL-1beta, IL-6, TNF-alpha), as well as neutrophil elastase secretion and beta-thromboglobulin release from platelets and S100 protein assay were performed. Serial blood samples were taken prior to the onset, after initiation, at the end and after weaning of the CPB; further samples were collected 6 and 24h after the end of the CPB. RESULTS: All patients were similar with regards to pre- and intra-operative characteristics and clinical outcomes were comparable for both groups. MECC system allowed a reduced hemodilution with a mean drop of the hematocrit of 8.5 vs. 15.3% (P<0.05). Mononuclear phagocytes dropped in a more important manner under standard CPB conditions (247+/-151 vs. 419+/-168, P=0.002), but both groups demonstrated a rise in monocyte count at the end of the CBP. No significant release of IL-1beta was observed in either group. By the end of CPB, IL-6 levels were significantly lower in the MECC group (38.8+/-19.6 vs. 87.9+/-78.9, P=0.04), despite a higher monocyte count. Plasma levels of TNF-alpha rised significantly more during standard CPB than with the MECC system (17.8+/-15.4 vs. 10.1+/-5.6, P=0.002). With MECC, the neutrophil elastase release was reduced (72.7+/-47.9 vs. 219.6+/-103.4, P=0.001). Platelet count remained at higher values with the minimal compared to standard CPB. It is noteworthy to consider that beta-thromboglobulin levels showed slightly lower platelet activation in the MECC group at all times of CPB (110.5+/-55.6 vs. 134.7+/-46.8, P=0.10). The pattern of release of S100 protein showed higher values in patients undergoing standard CPB than after MECC. CONCLUSIONS: The MECC system is suitable to maintain total extracorporeal circulation and demonstrates a lower inflammatory reaction when compared to standard CPB.

Totally minimized extracorporeal circulation: an important benefit for coronary artery bypass grafting in Jehovah's witnesses.

BACKGROUND: Jehovah's Witnesses who require cardiac surgery represent a challenge to the physician because of their refusal to accept blood transfusions. Because coronary artery bypass grafting (CABG) is performed by most surgeons under cardiopulmonary bypass (CPB), which has potentially deleterious effects on hemostasis, we used a new concept called minimal extracorporeal circulation (MECC). MECC includes heparin-coated tubing, a centrifugal pump, and an oxygenator. There is no venous reservoir or vent, and suction is used through the cell saver. We assessed the hypothesis that MECC in combination with low-volume blood cardioplegia preserves more hemoglobin than conventional CPB in standard CABG. METHODS: In 40 patients of the Jehovah's Witnesses faith undergoing CABG with the use of MECC and intermittent warm blood cardioplegia, clinical and biological data as well as values for parameters of hemolysis (plasma hemoglobin) and myocardial damage (troponin T) were determined. The results were compared with those of a control group of 40 patients who underwent operations with standard CPB. RESULTS: Demographics, hemodynamics, the number of anastomoses, and CPB and cross-clamp times were comparable between the groups. MECC patients demonstrated significantly lower peak levels of plasma hemoglobin (21.8 +/- 114 mg/dL versus 35.4 +/- 15 mg/dL) and troponin T (0.12 +/- 0.4 ng/mL versus 0.65 +/- 0.7 ng/mL), a higher minimum hematocrit level during CPB (30% +/- 7% versus 23% +/- 6%), and a higher hemoglobin level 2 days after surgery (13 +/- 3 g/100 mL versus 9.4 +/- 0.98 g/100 mL). Preoperative values were not significantly different. CONCLUSION: The use of MECC instead of conventional CPB reduces hemolysis, hemodilution, blood loss, and myocardial damage.