Status of permanent cardiac replacement for end-stage congestive heart failure

Permanent replacement of the heart in patients with end-stage congestive heart failure has long been sought after as the most definitive solution to an ever-growing problem. While cardiac transplantation is an effective therapy for many patients with end-stage congestive heart failure, this potential has been limited by the donor organ shortage and other limitations of long-term survival inherent in cardiac transplantation. While research anddevelopment of the total artificial heart continues to be of considerable interest, present-day mechanical circulatory support most commonly involves the use of left ventricular assist devices as a bridge to transplantation. Pneumatic and electromechanical pumps are now commonly employed in modern transplant practices with excellent hemodynamic function. The TCI HeartMate left ventricular assist device is now approved by the Food and Drug Administration for clinical implantation, with excellent preliminary results. Advances in the area of temporary and extended mechanical circulatory support are crucial to the ultimate development of a totally implantable artificial heart.     

Management of immediate graft failure after cardiac transplantation using cardiopulmonary bypass and intraaortic balloon-pumping followed by cardiac retransplantation

A 37-year-old man underwent cardiac transplantation for diffuse coronary artery disease and malignant arrhythmias. During the harvesting of the donor heart slight distention of the left ventricle was present due to insufficiency of the aortic valve. After explantation of the graft, fusion of 2 cusps was found and a commissurotomy of the aortic valve was performed and the graft transplanted. Despite maximum inotropic support immediate graft failure and aortic insufficiency was present and discontinuation of cardiopulmonary bypass (CPB) was impossible. After replacement of the aortic valve using a bioprosthesis and implantation of an intraaortic balloon-pump, low cardiac output persisted and CPB had to be continued. After 11 hours of normothermic cardiopulmonary bypass and intraaortic balloon-pumping a second graft became available and was retransplanted successfully. The postoperative course was uneventful and the patient remains well 3 months after the operation.     

Use of milrinone in cardiac surgical patients

Summary Milrinone is shown in 10 patients to be a valuable pharmacological bridge to heart transplantation; it can stabilize and improve decompensated chronic heart failure (CHF) in cases where the response to beta-agonists is inadequate. One patient who had suffered an acute myocardial infarction with heart failure resistant to vasodilators, beta-agonists, and balloon counterpulsation was stabilized with milrinone for 21 days. He was then maintained on ACE inhibitors until heart transplantation 3 months later. The other nine patients with severe decompensated CHF were stabilized on milrinone for between 11 and 51 days. Seven of them received a donor heart. Two patients died of bacteremic shock and terminal heart failure before a suitable organ could be found (31 and 51 days). All patients were clinically improved within 48 hours of the addition of IV milrinone to their therapy. In 55 patients following cardiac surgery, the efficacy and safety of milrinone in the treatment of low cardiac output states is demonstrated. Milrinone has a useful role in the management of patients with circulatory failure both before and after cardiac surgery, and this paper reviews the relevant current literature.     

Heart Transplantation in Perspective

Abstract Heart disease remains one of the leading causes of death in the western world. In the 35 years since the first human heart transplants, cardiac transplantation has become established as the therapeutic option of choice in the management of terminal cardiac failure. Since 1981, the introduction of cyclosporin for immunosuppression has dramatically increased cardiac transplantation. However, several obstacles limit further utilization, including limited availability of donor hearts, limited ischemic time tolerated by donor hearts, and chronic rejection. Research is underway into donor heart preservation and new immunosuppressant drugs in an effort to increase donor organ availability. Due to these constraints, alternative therapies are under development. More than 2,000 circulatory assist devices have been implanted with > 25% used as a bridge to heart transplantation. The University of Ottawa Heart Institute began the first Canadian implantation of circulatory assist devices in 1986 and has implanted 23 total artificial hearts and 23 ventricular assist devices. The Heart Institute is also developing a totally implantable electro-hydraulic ventricular assist device (EVAD) for long-term mechanical support outside the hospital. Another alternative being evaluated for clinical use is xenotransplantation. The major obstacle for widespread use of clinical xenotransplantation remains graft rejection, and fundamental research is ongoing to address hyperacute and delayed xenograft rejection. While cardiac tran-plantation is the most effective treatment of terminal heart failure, limited donor hearts compel us to rely on alternatives. In the future, the research underway on xenotransplantation and mechanical circulatory assist devices will provide new options for the clinical treatment of terminal cardiac failure.     

First use of the TandemHeart percutaneous left ventricular assist device as a short-term bridge to cardiac transplantation

Advanced heart failure may be refractory despite aggressive support with inotropic agents and intra-aortic balloon pumping. Implantable left ventricular assist devices are increasingly being used as bridges to cardiac transplantation or as destination therapy because of the limited availability of donor organs. We report the 1st use of the TandemHeart percutaneous ventricular assist device as a short-term bridge to cardiac transplantation.     

CsA对大鼠移植心脏细胞凋亡的影响

目的 :探讨细胞凋亡与心脏移植急、慢性排斥反应之间的关系。方法 :Wistar大鼠为供体 ,SD大鼠为受体 ,心脏移植术后给予环孢霉素A(CsA)治疗 ,在移植术后的不同时间 ,取下移植心脏 ,流式细胞术测定移植心脏组织的细胞凋亡率。结果 :CsA治疗的慢性排斥反应组 ,移植心脏的细胞凋亡率显著增高。结论 :细胞凋亡参与移植排斥反应 ,移植心脏细胞凋亡率的检测可作为诊断排斥反应和移植物能否长期存活的指标之一。     

大鼠移植心脏存活的长期观察

目的 :观察大鼠移植心脏存活的长期变化 ,为心脏移植的实验研究提供依据。方法 :采用供体脾细胞 (SPC)和环磷酰胺 (CP)预处理移植受体 ,然后行大鼠颈部心脏移植术 ,根据实验分组进行术后观察。结果 :SPC和CP预处理后 ,移植心脏的存活时间明显延长 ,在术后 7～ 10天移植心脏增大 ,心肌收缩力减弱 ,心律变慢 ,15天以后移植心脏功能逐渐好转。结论 :SPC和CP治疗可以诱导受体对移植物的免疫耐受 ,只要受体存活 ,移植心脏不需要每日视诊或触诊检查     

Influence of pre-existing donor atherosclerosis on the development of cardiac allograft vasculopathy and outcomes in heart transplant recipients.

OBJECTIVES: This study sought to evaluate the influence of donor lesions on the development of cardiac allograft vasculopathy and outcomes in heart transplant recipients. BACKGROUND: After orthotopic heart transplantation (OHT), coronary artery narrowing occurs as a combination of pre-existing donor lesions and new lesions that develop as a result of cardiac allograft vasculopathy. METHODS: Intravascular ultrasound (IVUS) studies were performed in 301 recipients at 1.3 +/- 0.6 months and again at 12.2 +/- 0.8 months after OHT. Additional IVUS studies were performed in 90 patients at two and three years of follow-up. Sites at baseline with maximum intimal thickness > or =0.5 mm were defined as pre-existing donor lesions. The angiographic diagnosis of transplant coronary artery disease (TCAD) was defined as a new > or =50% diameter narrowing of a major epicardial vessel. RESULTS: Donor lesions were present in 30% of the hearts. By IVUS, sites with donor lesions did not have a greater increase in intimal area compared with sites without donor lesions. Angiographically, the incidence of TCAD up to three years after transplantation was higher in recipients with donor lesions than in recipients without donor lesions (25% vs. 4%, p < 0.001). However, the three-year mortality rate was similar between recipients with or without donor lesions (4.5% vs. 5.2%, p = 1.0). CONCLUSIONS: Pre-existing donor lesions do not act as a nidus for accelerating the progression of intimal hyperplasia. However, patients with donor lesions have a higher incidence of angiographic TCAD. Donor lesions do not affect the long-term survival of patients with OHT up to three years.     

Trends in cardiovascular medicine: Update on cardiac transplantation

Advanced heart failure affects more than 250,000 people in the United States alone and is associated with high risk of morbidity and mortality. Cardiac transplantation provides a cure for patients with advanced disease but has historically been limited by donor availability. Recent changes in the allocation system as well as advances in donor selection, procurement and desensitization protocols have served to widen the donor pool and increase the availability of cardiac transplantation for those in need. This review provides an update on recent advances in cardiac transplantation.     

The need for artificial hearts.

Chronic immunosuppression, allograft coronary disease, and restricted availability of donor organs continue to limit the scope of cardiac transplantation. Meanwhile increasingly favourable experience with implantable blood pumps used as a bridge to transplant has reintroduced the concept of permanent mechanical cardiac support. Existing models (for example, the Thermo Cardiosystems Heartmate device) are now used for such support in patients who are not candidates for transplantation. Miniaturised axial flow pumps such as the Jarvik 2000 fit within the failed left ventricle and provide an exciting prospect for the treatment of heart failure in the future. Preliminary experience suggests that the "offloaded" left ventricle may recover. Mechanical blood pumps can be used before the onset of multisystem failure and removed if the myocardium recovers. This "bridge to recovery" concept should be tested in patients with recoverable cardiomyopathy and those with coronary disease and poor left ventricular function where an implantable pump can be used in conjunction with myocardial revascularisation.     

Human Embryonic Stem Cells vs Human Induced Pluripotent Stem Cells for Cardiac Repair

Human embryonic stem cells (hESCs) and human induced pluripotent stem cells (hiPSCs) have the capacity to differentiate into any specialized cell type, including cardiomyocytes. Therefore, hESC-derived and hiPSC-derived cardiomyocytes (hESC-CMs and hiPSC-CMs, respectively) offer great potential for cardiac regenerative medicine. Unlike some organs, the heart has a limited ability to regenerate, and dysfunction resulting from significant cardiomyocyte loss under pathophysiological conditions, such as myocardial infarction (MI), can lead to heart failure. Unfortunately, for patients with end-stage heart failure, heart transplantation remains the main alternative, and it is insufficient, mainly because of the limited availability of donor organs. Although left ventricular assist devices are progressively entering clinical practice as a bridge to transplantation and even as an optional therapy, cell replacement therapy presents a plausible alternative to donor organ transplantation. During the past decade, multiple candidate cells were proposed for cardiac regeneration, and their mechanisms of action in the myocardium have been explored. The purpose of this article is to critically review the comprehensive research involving the use of hESCs and hiPSCs in MI models and to discuss current controversies, unresolved issues, challenges, and future directions.     

The impact of mode of donor brain death on cardiac allograft vasculopathy: an intravascular ultrasound study

OBJECTIVES: We evaluated the association of mode of brain death with cardiac allograft vasculopathy. BACKGROUND: Explosive brain death (EBD) is accompanied by a sudden increase in intracranial pressure, with recruitment of pro-inflammatory cytokines, as well as adhesion cell and co-stimulatory molecules. Whether these early events influence the later development of cardiac allograft vasculopathy following heart transplantation remains unknown. METHODS: An inception cohort of 61 consecutive heart transplant recipients between 1993 and 1995 who underwent intravascular ultrasound examination of the coronary arteries were evaluated. Based on the mode of donor brain death, this cohort was divided into either an EBD group (n = 27) or non-EBD (n = 34), and the development of intimal thickness and cardiac events (sudden cardiac death, myocardial infarction, and need for coronary revascularization via percutaneous techniques or surgical bypass) was assessed. RESULTS: Despite similar posttransplant survival and distribution of nonimmunological and immunological variables, heart transplant recipients with EBD demonstrated greater intimal thickening (0.59 +/- 0.1 vs. 0.32 +/- 0.2 mm; p = 0.02) and higher cardiac events (37% vs. 12%; p = 0.01) when compared to those with non-EBD donors. Hearts from donors with EBD had lower survival (63 +/- 19 vs. 72 +/- 17 months) than with non-EBD donors (p = 0.04). CONCLUSIONS: Explosive brain death is a significant determinant for the late development of cardiac allograft vasculopathy and influences long-term allograft survival. Thus, strategies focusing on limitation of vascular allograft injury in the pre-engraftment phase of cardiac transplantation are warranted.     

Current status of cardiac transplantation and mechanical circulatory support

Cardiac transplantation and mechanical circulatory support are possible options for improving survival and quality of life in patients with isolated cardiac disease and end-stage heart failure. Transplantation is limited by donor availability but has a median survival of 10 years. Post-transplant immunosuppression is often transplant center dependent, but a tacrolimus and mycophenolate mofetil-based regimen may be preferred. Sirolimus may reduce the progression rate of transplant vasculopathy. There has been a trend toward continuous-flow left ventricular assist devices because of their increased durability and reduced size. A variety of surgical and percutaneous ventricular assist devices may be used as a bridge to decision on a patient’s candidacy for transplantation. Mechanical circulatory support as destination therapy has not been widely implemented because of poor device durability, but this is expected to change with newer devices. Mechanical circulatory support as a bridge to myocardial recovery has been successful only in a few patients.     

Role of cytomegalovirus in cardiac allograft vasculopathy

Cardiac allograft vasculopathy is the most common cause of death and retransplantation following heart transplantation, and about 10% of patients per year have evidence of accelerated vascular disease; 50% at 5 years. Cytomegalovirus (CMV) infection has been associated with accelerated cardiac vasculopathy and decreased 5-year survival. Prophylactic therapy using ganciclovir has reduced the incidence of CMV disease, but not in the group at highest risk, namely the seronegative recipient of an allograft from a seropositive donor (D+/R–). Combination prophylaxis consisting of CMV hyperimmune globulin (CMV-IGIV) plus ganciclovir is associated with decreased intimal thickening, reduced coronary artery disease and obliterative bronchiolitis, and improved survival.     

The feasibility of left ventricular mechanical support as a bridge to cardiac recovery

OBJECTIVE: To study the achievability of device weaning in patients receiving left ventricular assist devices (LVADs) as a bridge to transplantation. METHODS: Eighteen consecutive patients receiving a LVAD between September 1997 and June 2002 were included in the study. During a four-month follow-up, patients were repeatedly evaluated with right heart catheterization and echocardiography and, if functional improvement was observed, studied with the device turned off. Cardiac recovery was defined as off-pump LVEF>or=40% together with a significant improvement in invasive haemodynamic measurements (CI>or=2.5 and PCWP相似文献   

When is Retransplantation a Viable Option?

As the number of recipients of heart transplantation grows over time and they survive longer, more are at risk for developing severe cardiac allograft vasculopathy and allograft dysfunction, which might lead to consideration for retransplantation. Clearly, outcomes following cardiac retransplantation are compromised, and with donor shortage, the selection of candidates must be judicious. Retransplantation appears most appropriate for those patients more than 6 months following original heart transplantation, who have severe cardiac allograft vasculopathy and associated left ventricular dysfunction, or allograft dysfunction and progressive symptoms of heart failure in the absence of acute rejection. Relative contraindications to transplantation (ie, advanced age, comorbidities, psychosocial issues) require thorough assessment when retransplantation is being considered.     

连续灌注不停跳心脏移植对供心的保护作用

目的 通过建立大鼠同种异位供心停跳心脏移植模型与连续血液灌注供心不停跳心脏移植模型,探讨连续灌注不停跳心脏移植对供心的影响.方法 建立大鼠同种异位连续灌注心脏不停跳心脏移植模型（不停跳移植组）和改良Heron法建立大鼠异位心脏移植模型（停跳移植组）.移植成功后2h检测受体外周血肌酸激酶同工酶（CK-MB）和心肌肌钙蛋白I（cTnI）含量,测定供心心肌脂质过氧化终产物丙二醛（MDA）、过氧化物歧化酶（SOD）含量,电镜观察心肌结构变化,并观察心肌凋亡情况.结果 连续灌注心脏不停跳移植组受体外周血CK-MB及cTnI含量低于停跳移植组,差异有统计学意义（P＜0.05）.与停跳移植组比较,不停跳移植组心肌MDA含量相对较少,SOD含量相对较多,心肌细胞凋亡指数较小,差异均有统计学意义（P＜0.05）.不停跳移植组心肌线粒体等结构损伤相对较轻.结论 心脏不停跳技术能有效减轻心脏移植供心的脂质过氧化反应,保护心肌线粒体,抑制心肌细胞凋亡,可减轻心脏移植供心的再灌注损伤.     

Ventricular arrhythmias in long term survivors of orthotopic and heterotopic cardiac transplantation.

Fourteen long term survivors with orthotopic (recipient heart replaced by donor heart) and nine with heterotopic cardiac transplants (recipient heart retained) had 24 hour ambulatory electrocardiographic monitoring to detect ventricular arrhythmias. Arrhythmia was uncommon in the patients with orthotopic transplants; none of them had more than one extrasystole per hour. In the patients with heterotopic cardiac transplants the recipient's own heart showed significantly more frequent ventricular arrhythmias than the corresponding donor heart: abnormal complexes (mean/24 h) 4583 vs 42.7; extrasystoles 1772 vs 17.8; pairs 121 vs 0.8. There was no relation between the abnormal ventricular activity of the two hearts in the patients with heterotopic transplants on a beat by beat, hourly, or 24 hour basis. There was no consistent diurnal variation in the frequency of the abnormal ventricular beats after cardiac transplantation. The occurrence of ventricular arrhythmia was unrelated to the interval from operation to the study. In long term survivors of cardiac transplantation the denervated heart shows a little ventricular ectopic activity even when compared with normal hearts. In patients with heterotopic transplants ventricular arrhythmias commonly occur in the recipient's own heart; these are probably related to the underlying severity of the original disease.     

The recipient becomes a donor: Allograft aortic valves from the excised hearts of cardiac transplant patients

Background: The indications for aortic valve replacement with an allograft valve are well established, but the availability of such valves is limited. A potential source is from the excised hearts of patients undergoing heart transplantation (HTX). Methods: The retrieval and use of allograft aortic valves taken from the 85 excised hearts of HTX recipients during 1987–1997 was reviewed. Freedom from death or reoperation and the functional status of the recipients of these allograft valves were determined. Results: Seventeen allografts (20%) from HTX patients were used, accounting for 2.7% of the total allografts implanted (n=620). Two cryopreserved valves remained available for implantation, and 2 were being processed. In addition, one was thawed in theatre and not used. Reasons for not retrieving the remaining valves were: hearts not inspected or no record (34), valves did not meet selection criteria (21), valves damaged during excision (7) and prosthetic valve in aortic position (1). Establishment of a more rigorous routine in the past 5 years has improved retrievals by reducing the first reason. For the 17 recipients (mean age 47, range 19–83), allograft valves were chosen because: warfarin undesirable (7), small aortic root (4), old age (3), endocarditis (2), root replacement (1). At a mean of 49 months after implantation, 15 patients were alive (4-year freedom from death 85%). One further patient had undergone elective replacement with a prosthetic valve (4-year freedom from death or valve replacement 79%). The NYHA functional class was I in 14 patients and H in 1. Conclusions: Aortic valves from HTX patients' excised hearts are a small but valuable and important potential source of allografts. Knowledge that a part of their diseased heart may be used to treat another patient may help HTX patients endure the emotional stresses of transplantation.     

A heart failure specialist’s perspective on cardiac surgery for heart failure

Aside from cardiac transplantation, ventricular assist devices, and the total artificial heart, cardiac surgery now also plays a major role in the overall management of the heart failure patient. For patients with heart failure, cardiac surgery has steadily moved from being a predominant rescue procedure (eg, aneursymectomy, rupture repair, transplantation) to surgical interventions that can prevent or delay the progression of cardiac dysfunction and failure; these operations now include coronary artery bypass surgery, ventricular restoration, and valvular repair/replacement. This article discusses the role and impact of these specific surgical interventions in the setting of ventricular dysfunction and heart failure.