心脏移植术后冠状动脉病变的相关因素分析

目的探讨心脏移植术后长期存活的患者冠状动脉病变的相关危险因素。方法回顾性分析32例心脏移植术后长期存活患者的临床资料,并对相关的临床因素进行评价,筛选出移植心冠状动脉病变的独立危险因素。结果高脂血症、热缺血时间、巨细胞病毒(CMV)抗体阳性、移植后时间及慢性排斥反应是移植心冠状动脉病变的危险因素,而年龄、高血压和糖尿病与移植心冠状动脉病变的相关性不明显;多元Losgitic回归分析,移植后时间和慢性排斥反应是移植心冠状动脉病变的独立危险因素(P<0.001,P=0.003)。结论心脏移植术后冠状动脉病变的实质是慢性排斥反应;与供心的热缺血时间、高脂血症及巨细胞病毒感染等相关。     

Intragraft heme oxygenase-1 and coronary artery disease after heart transplantation

Peri-operative tissue injury triggers the development of Transplant Coronary Artery Disease (TCAD). Animal studies have shown that induction of heme oxygenase (HO)-1 protects the donor organ from the development of TCAD. To investigate the role of HO-1 in TCAD after clinical heart transplantation, we measured intragraft mRNA expression of HO-1, HIF-1alpha, TGF-beta, FLIP, and the Bcl-2/Bax balance. Immunohistochemical staining of HO-1 was performed to determine its origin. Myocardial biopsies taken at the end of the transplantation procedure (time 0), at 1 week and at 10 months after transplantation were studied from recipients with or without angiographic signs of accelerated TCAD, diagnosed after 1 year. At time 0, no differences in mRNA expression for any of the measured parameters were found between TCAD positive and negative patients. At 1 week, mRNA expression of HO-1 and TGF-beta was higher in grafts that developed accelerated TCAD (p=0.001 and p=0.0002). These higher mRNA levels were accompanied by a pro-apoptotic shift in Bcl-2/Bax (p=0.02), suggesting proneness for apoptosis via the mitochondrial pathway. Immunohistochemical staining showed that HO-1 was mainly produced by infiltrating macrophages. At 10 months, again HO-1 and TGF-beta levels were high in TCAD positive patients (p=0.02 and p=0.05), but the expression of apoptotic markers was comparable at this time point. Our results suggest that a higher HO-1 by macrophages in our patient population might be an adaptive response to tissue injury and inflammation, reflecting damage due to the transplantation procedure that finally results in TCAD.     

Beating heart coronary artery bypass surgery after orthotopic heart transplantation

Beating-heart coronary artery bypass surgery was performed in a 52-year-old man with accelerated transplant coronary artery disease 10 years after orthotopic heart transplantation. Transplant coronary artery disease was first detected in the left circumflex coronary artery 9 years after transplantation. Rapid progression to triple vessel disease occurred within 1 year, and the patient developed worsening symptoms of shortness of breath and chest pain. He underwent off-pump "beating heart" left internal mammary artery to left anterior descending coronary artery bypass surgery. The circumflex coronary artery was not graftable due to diffuse and truncated small vessel disease. His postoperative course was uneventful and he was discharged on the fifth postoperative day. Coronary angiography 3 months after the surgery revealed a widely patent left internal mammary artery to left anterior descending artery bypass. He is alive and symptom free more than 1 year after his surgery.     

Non-invasive evaluation of orthotopic heart transplant rejection by echocardiography.

BACKGROUND: Heart transplant recipients require frequent myocardial biopsies to screen for acute rejection. The purpose of this study was to identify demographic and echocardiographic factors associated with transplant rejection and develop a predictive model, which may reduce the number of cardiac biopsies. METHODS: From January 1998 to December 2001, we performed 406 echocardiographic studies on 264 heart transplant patients who had biopsies performed on the same day. Two-dimensional, pulsed and tissue Doppler echocardiographic variables were compared between patients with and without rejection, and their predictive ability for detecting rejection was determined by uni- and multivariate analyses. RESULTS: In 268 biopsies there was no significant rejection (ISHLT Grade <==II), whereas 138 showed rejection (ISHLT Grade > or =IIIa). By multivariate analysis, pericardial effusion, isovolumic relaxation time (IVRT) <90 milliseconds and mitral inflow E/A ratio >1.7, diameter of inferior vena cava and duration of pulmonary vein atrial reversal were independently associated with rejection. Because the odds ratios were similar for all 5 predictors, a simplified model was developed based on the sum of the number of abnormal predictors present (0 to 5). The probability of rejection increased from 15.9%, in the absence of any predictor, to 39.7%, 52.0% and 71.1%, if 1, 2 or 3 predictors were present, respectively. CONCLUSIONS: Recipient age, pericardial effusion, IVRT and ratio of pulsed Doppler E/A are significant predictors of acute cardiac allograft rejection. However, no single predictor or combination of predictors were powerful enough to eliminate surveillance endomyocardial biopsies.     

Pravastatin prevents the progression of accelerated coronary artery disease after heart transplantation in a rabbit model

Abstract  This study was designed to investigate the effects of pravastatin (Pr) on accelerated coronary arteriosclerosis in transplanted hearts. The rabbit hearts were transplanted to the recipients' neck heterotopi-cally, and received FK506. The rabbits in group 1 were fed a normal diet (ND), and cholesterol-rich diet (CD) in group 2 and 3. Pr (10 mg/kg) was given to group 3. They were sacrificed at 4 weeks and the severity of m%cardial rejection and arteriosclerosis was assessed and scored histologically. The serum lipid levels were significantly elevated by a CD. However, addition of Pr had no effect on the levels of LDL and total cholesterol (TC). There was no significant difference in m%cardial rejection in each group. Transplanted hearts in group 2 showed more severe arteriosclerotic lesions than those in group 1. Pr treatment in group 3 diminished the severity of coronary arteriosclerosis. Pr may prevent the accelerated coronary arteriosclerosis after heart transplantation without significant changes in TC and LDL.     

The influence of rejection episodes on the development of coronary artery disease after heart transplantation

Since 1981, 77 of 116 patients undergoing heart transplantation (HTx) have survived from 6 months to 8 years. Graft control involved a total of 871 endomyocardial biopsies (EMB) and 141 angiographies. Sixteen patients developed coronary artery disease (CAD) manifesting itself 7-60 months after HTx (20.7%). These patients (15 male, 1 female) experienced multiple rejection episodes (RE) and more than half suffered from hypercholesterolaemia and hypertension (n = 10). A mean rejection score (Billingham grading) of greater than 1 (mean = 1.6 +/- 1.1) was calculated in all patients with CAD at the time of angiography or autopsy. By contrast, the mean rejection score ranked less than 1 in patients with undetectable or resolved CAD (means = 0.4 +/- 0.38). This rate is not remarkably different from the rejection score in patients (n = 61) without CAD (mean = 0.2 +/- 0.4). The 8 patients alive (56 +/- 18 months) showed a low number of RE/year (mean = 1.1 +/- 0.4) compared with means = 1 +/- 0.9 in patients without CAD. Eight patients expired within a short period (mean = 31 +/- 26.9) and had a significantly higher number of RE/year (mean = 4.3 +/- 2.9; P less than 0.01 vs. no CAD, CAD alive). Autopsy (n = 6) and angiographic studies (n = 46) demonstrated diffuse, concentric, obliterative arterial disease in all vessels (type A) in 6 patients (RE/yr: mean = +/- 5.5 +/- 2.3), single stenoses in major coronary vessels (type B) in 7 patients and ordinary atherosclerosis (3-vessel disease) comparable to ischaemic heart disease (type C) in 3 patients.(ABSTRACT TRUNCATED AT 250 WORDS)     

Late pacemaker requirement after pediatric orthotopic heart transplantation may predict the presence of transplant coronary artery disease.

BACKGROUND: Few data are available regarding pacemaker implantation after pediatric orthotopic heart transplantation. The purpose of this study was to assess the incidence, indications and associations with regard to pacemaker placement in children who have undergone orthotopic heart transplantation. METHODS: We performed a retrospective study of all patients undergoing orthotopic heart transplantation at our institution from October 1984 to March 2001. Data obtained included demographics, indications for pacemaker, presence of transplant coronary artery disease and long-term follow-up. Patients were divided into: Group 1, patients requiring a pacemaker within 3 months of transplantation; and Group 2, patients requiring a pacemaker beyond 3 months. RESULTS: Pacemakers were required in 7 of 106 (6.6%) transplant recipients. Pacing indications for patients in Group 1 (n = 2) were persistent bradycardia with pause-related ventricular arrhythmia and atrial flutter with resultant sinus pauses of up to 4 seconds. In Group 2 patients (n = 5), indications for pacing were high-grade atrioventricular (AV) block in 1 patient and episodic sinus pauses up to 3.3 seconds associated with syncope/dizziness in the remaining 4 patients. All patients in Group 2 had transplant coronary disease diagnosed within 1 year of pacemaker implantation. All had resolution of symptoms and no complications after implantation. CONCLUSIONS: Pacemakers are infrequently required after cardiac transplantation in children. Despite not meeting classic symptomatic sinus bradycardia criteria, pacemaker placement should be considered post-transplantation in patients with episodic sinus pauses and dizziness or syncope. Patients who present with the aforementioned symptoms or high-grade AV block should be evaluated closely for the presence or development of transplant coronary artery disease, as it may be their first symptom.     

L-arginine polymer mediated inhibition of graft coronary artery disease after cardiac transplantation.

BACKGROUND: Nitric oxide (NO) limits the development of graft coronary artery disease (GCAD) in transplanted hearts. We hypothesized that l-arginine polymers administered to cardiac allografts ex vivo would translocate across vascular cellular membranes, up-regulate inducible nitric oxide synthase (iNOS) production of NO, and inhibit the development of GCAD. METHODS: Three groups of PVG rat donor hearts were incubated with either 0.8 ml phosphate-buffered saline, (PBS, n=12) or 50 microM L-arginine polymer solutions of length five (R5, n=12) or nine (R9, n=12) prior to heterotopic transplantation into ACI recipients. Graft vessels were scored at POD 60 and 90 for percentage luminal narrowing (%LN), intima to media ratio (I/M), and percentage affected vessels (%AV). Translocation efficiency was determined by treatment with biotinylated polymers. NO production of treated aortic segments was determined in vitro by Griess reaction. RESULTS: Translocation efficiencies were 89+/-19% (R9), 7+/-10% (R5), and 0+/-0% PBS (ANOVA, P<0.001) which corresponded to NO production in treated aortic segments of 0.175+/-0.17 (R9), 0.120+/-0.006 (R5), and 0.135+/-0.035 microM/mg (PBS), (ANOVA, P=0.002). GCAD scores at POD 60 were: %LN: 3.2+/-3.8% (R9), 12.6+/-6.7% (R5), 11.3+/-4.2% (PBS) (ANOVA, P=0.025); I/M: 0.03+/-0.04 (R9), 0.13+/-0.07 (R5), 0.12+/-0.05 (PBS) (ANOVA, P=0.037); %AV: 7+/-7% (R9), 19+/-7%(R5), 22+/-9%(PBS) (ANOVA, P=0.021). Reduction of GCAD parameters was maintained at POD 90. CONCLUSION: R9 efficiently translocated across cytoplasmic membranes, enhanced vascular NO production, and decreased neointimal hyperplasia. This ex vivo treatment may have a therapeutic role in preventing GCAD.     

血管紧张素转换酶抑制剂对心脏移植后冠状血管增殖病变的影响

目的通过建立大鼠心脏移植后冠状血管增殖病变的模型,观察血管紧张素转换酶抑制剂(ACEI)对心脏移植后冠状血管增殖病变的影响。方法设立对照组、结扎组、ACEI+结扎组,观察2周后各组大鼠血液、心肌AngⅡ含量,心肌AngⅡ受体密度,及血管病理学结果。结果各组血液AngⅡ含量差异无统计学意义,结扎组心肌AngⅡ含量明显增高(17．42±5．49)fmol／mg．蛋白P<0．001比对照组,ACEI+结扎组AngⅡ含量明显下降(5．35±1．95)fmol／mg。蛋白P< 0．01比结扎组,结扎组AngⅡ受体密度增高(48．80±4．32)fmol／mg蛋白P<0．01比对照组,ACEI +结扎组内膜增生比结扎组明显减轻[内膜厚度(21．01±4．55)μm比(60．34±9．32)μm,P< 0．01)。结论心脏局部肾素-血管紧张素系统,AngⅡ及AngⅡ受体参与移植后冠状血管病变,A- CEI明显抑制移植后冠状血管病增殖变。     

Coronary artery to pulmonary artery collaterals after heart transplantation.

Collaterals are described between coronary and pulmonary arteries after orthotopic heart transplantation. It is likely the collaterals developed as a result of adhesions in the pericardial space. This is a previously unrecognized complication of heart transplantation with potential clinical implications, as coronary to extracardiac artery collaterals have been shown to cause myocardial ischemia.     

Diagnosis of coronary artery disease by stress echocardiography and perfusion scintigraphy

This meta-analysis was performed to compare the diagnostic efficacy of stress echocardiography (SE) and Stress perfusion studies (SPS) in detecting coronary artery disease (CAD). A meta-analysis of peer reviewed articles, published in English language, reporting head-to-head comparison of vasodilator stress echocardiography (VSE) and SPS for the diagnosis of CAD, was performed. Data of 13 studies comprising of 860 patients from 13 different institutions were analyzed. Algorithms were developed to generate raw data from published papers to calculate statistical parameters with confidence intervals and then compare them at specified significance levels. The overall diagnostic accuracy of the two tests was almost similar, 0.77 for VSE vs 0.8 for SPS (p=ns). SPS gave higher sensitivity, 0.88 vs 0.70 in cumulative data (p<0.0001) while VSE gave higher specificity, 0.90 vs 0.67 (p<0.0001). Accuracy of VSE with state-of-the-art protocols became even better than SPS (p<0.05). In hypertensive patients specificity of SPS was markedly deteriorated. Contrary to this, VSE gave higher specificity (0.90 vs 0.40) in this subgroup of patients as well. VSE might become an effective alternative of SPS where scintigraphy techniques are not available or affordable.     

Impact of proximal or midvessel discrete coronary artery stenoses on survival after heart transplantation.

To assess survival after the development of transplant coronary artery disease, annual angiography reports from 353 heart transplant recipients were reviewed. Fifty-four patients who survived beyond 1 year and in whom moderate-to-severe proximal or midvessel coronary artery disease developed were identified. Moderate-to-severe proximal or midvessel coronary disease was defined for this study as a 40% or more stenosis in 1 or more primary or secondary epicardial arteries. Actuarial survival (Kaplan-Meier) from the time of disease detection in those 54 patients was 67% at 1 year, 44% at 2 years, and 17% at 5 years. Actuarial survival was reduced proportionate to disease severity. Survival for single-vessel disease (> or = 40% stenosis) was 64% at 1 year, 36% at 2 years, and 22% at 5 years. Survival was significantly worse with triple-vessel disease (13% at 2 years; p = 0.01) and intermediate for double-vessel disease (41% at 2 years; p = 0.01). Of 19 patients who underwent retransplantation for coronary artery disease, 13 patients (68%) died at a mean of 24 +/- 20 months (range, 1 to 59), and of 15 patients from whom postmortem or angiographic data were available, 11 patients (73%) showed recurrence of significant coronary artery disease in the new graft. Identification of moderate or severe proximal or midvessel coronary disease at angiography predicts an overall mortality rate of more than 50% at 2 years. The poor survival rate in those who underwent retransplantation (around 50% at 4 years) and the high rate of redevelopment of coronary disease suggest that retransplantation should be reserved for selected candidates with angiographically severe disease, if used at all.