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Cardiac replacement with a total artificial heart as a bridge to transplantationCopeland JG, Smith RG, Arabia FA, et al. N Engl J Med 2004; 351:859-67Reviewer: K.W. Tim Park, MD
Background: In the United States, there are nearly five million people with heart failure (HF), generating health care costs of over $38 billion.1 Each year, 550,000 new cases of HF are diagnosed and nearly 300,000 die of HF, among whom 15-25% die while waiting for transplantation.2 Whereas 30,000 - 70,000 Americans per year have been estimated to possibly benefit from cardiac transplantation,3 the annual national supply of donor hearts barely exceeds 2,0002 and the waiting time before transplantation exceeds a year. The rate of survival in those waiting for transplantation may be improved with the use of paracorporeal devices or ventricular assist devices, either implanted or extracorporeal. The CardioWest Total Artificial Heart is a biventricular, pneumatic, pulsatile pump that completely replaces the native ventricles and all four cardiac valves. It can deliver a cardiac output of > 9 liters per minute at maximal stroke volume of 70 cc. Because it is powered by a large console on wheels, the patient is bound to the hospital, though in Europe, portable drivers are currently in use. This device may be useful in those in whom ventricular assist devices may be contraindicated, including those with aortic regurgitation, a left ventricular thrombus, an aortic prosthesis, an acquired ventricular septal defect, or irreversible biventricular failure requiring high pump outputs. The current study reports on the 10-year experience with the CardioWest Heart. Methods: Patients were enrolled into the CardioWest Heart study prospectively from 1993 to September 2002 at five participating institutions. One hundred thirty study patients were compared to 35 historical controls, who were matched for the inclusion and exclusion criteria of the study, but had not received any mechanical circulatory support. The inclusion criteria were NYHA IV patients eligible for transplantation with body surface area of 1.7-2.5 m2 and hemodynamic insufficiency, while exclusion criteria were use of any vascular assist device, pulmonary vascular resistance > 640 dyn-sec/cm5, dialysis in previous 7 days, serum creatinine > 5 mg/dl, cirrhosis with total bilirubin > 5 mg/dl, and cytotoxic antibody >10%. The two groups were compared for baseline demographic, clinical, and laboratory parameters and for the end points of survival to transplantation, overall survival, survival after transplantation, and a composite parameter called "treatment success" defined as the patient being alive, ambulatory, in NYHA class I or II, and not dependent on a ventilator and dialysis 30 days after transplantation. Fisher's exact test was used for between-group comparisons of dichotomous variables and Kaplan-Meier analyses were used to compare time-to-event distributions. Results: The study and control groups differed significantly in 12 of 65 baseline characteristics. An ischemic cause of heart failure, history of smoking, use of anticoagulation, prior cardiac surgery, and current use of an intraaortic balloon pump were more common in the control group, whereas the use of cardiopulmonary bypass and the use of inotropic support were more common in the study group. The rate of survival to transplantation was significantly higher in the study group (79% vs. 46%, P < 0.001), even though the mean time from entry into the study to transplantation was much longer in the study group (79.1 days vs. 8.5 days, P < 0.001). The overall one-year survival rate, one- and five-year survival after transplantation were all significantly higher in the study group (70 % vs. 31 %, 86 % vs. 69 %, and 64 % vs. 34 %, respectively). Treatment success rate was 69 % in the study group, as compared with 37% in the controls (P = 0.002). In 14 patients who received an implant off-protocol, the rate of survival to transplantation was 50%. In the study group, patients' hemodynamic status improved significantly upon implantation of the artificial heart. Renal and hepatic function tests returned to normal within three weeks after implantation. The quality of life improved significantly with an implant, with 75% of the patients getting out of the bed within a week of implantation. The implant was used for a total of 6,407 days in the study group. There were 102 bleeding events, 55 occurring during implantation and two leading to death. Device malfunction led to a death 124 days after implantation and a poor fit contributed to death in two patients. There were 125 infections during the use of the artificial heart, causing death in one patient, contributing to death in seven, and delaying transplantation in five. There were 26 neurologic events, including 11 strokes in 10 patients, with half recovering within 48 hours and none resulting in deaths. There were three procedural complications in three patients, in whom the central venous catheter obstructed the mechanical tricuspid valve. Central venous catheters in the right atrium of the artificial heart are considered contraindicated. Discussion and Comments: The study has several limitations. One is that while the study patients were enrolled prospectively, they are compared retrospectively to a historical control group. Second, the study and control groups were not exactly matched, but differed in 12 of the 65 baseline characteristics. Thus, the control group did not provide the natural history of the study group patients without the artificial heart. Despite these limitations, it is apparent from the study that the artificial heart was able to improve the clinical picture prior to transplantation, thereby improving survival to transplantation. The rate of survival to transplantation of 79% with CardioWest Heart compares favorably with previous studies4-8 of approved devices that reported rates of 60-74% with left ventricular assist devices and 58-61% with biventricular assist devices. In addition, survival after transplantation appears to be better in those receiving the artificial heart, compared to the controls. Hemodynamic deterioration in cardiac transplant candidates is often followed by metabolic, cellular, and nutritional compromise and this diminishes the likelihood of survival after transplantation as well as survival to transplantation. As shown in this study, the timely use of mechanical circulatory support appears to stop and reverse metabolic deterioration and end-organ dysfunction and thereby improve survival after transplantation. Although CardioWest Heart is considered a bridge to transplantation and not a destination therapy, the question that will need to be answered in future studies is whether transplant candidates with metabolic compromise should first have a mechanical assist device before transplantation, even if a donor heart is immediately available. Use of the mechanical heart may improve the clinical condition of the transplant candidates sufficiently so that they improve their rate of treatment success and survival after transplantation. As emphasized in the editorial accompanying the article,9 the benefits of the bridge device may not be made any less obvious by any limitations of the study methodology. References
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