Incidence and clinical relevance of coronary calcification detected by electron beam computed tomography in heart transplant recipients.

BACKGROUND: Patients treated by cardiac transplantation who survive beyond one year are at significant risk from fatal coronary artery disease. The development of coronary artery calcification in these patients is discussed and methods available to detect it are reviewed. OBJECTIVES: To assess the clinical importance of coronary artery calcium in heart transplant recipients. METHODS: In a cohort of 102 cardiac transplant recipients, electron beam computed tomography was used to measure calcium in the coronary arterial wall 63 days to 9.1 years (median 4.6 years) after transplantation. The results were compared with angiographic findings and with conventional coronary disease risk factors. The patients were followed for a mean of 2.12 years (1.2-4.02 years) to assess the relationship between these findings and future cardiac events. RESULTS: Forty-one (40.2%) had a stenosis of > 24% in one or more major coronary artery at angiography. Forty-six (45%) had a coronary calcium score > 0. The absence of calcium had a negative predictive value with respect to angiographic disease in any vessels of 87.5%. Logistic regression revealed that dyslipidaemia, systemic hypertension and organ ischaemic time were significant predictors of calcification. At follow-up, both an abnormal coronary angiogram and coronary calcium were found to be the only significant predictors of late events. Multivariate analysis suggested that the detection of coronary calcium did not offer any additional predictive information over that provided by the angiogram itself. CONCLUSION: Electron beam computed tomography is well suited to the assessment of calcium in the coronary arteries of heart transplant recipients, although the mechanisms of this calcification remain poorly understood. Calcium is detected more frequently than would be suggested by studies using intravascular ultrasound. It is associated with the presence of angiographic disease, and with some conventional risk factors for coronary disease. At follow-up the presence of coronary calcium was associated with an adverse clinical outcome, as it is in conventional ischaemic heart disease.

Donor ACE gene polymorphism: a genetic risk factor for accelerated coronary sclerosis following cardiac transplantation.

AIMS: To investigate the role of angiotensin converting enzyme (ACE) (I/D) gene polymorphism in the development of coronary sclerosis after cardiac transplantation. METHODS AND RESULTS: Eighty cardiac transplant recipients (44 transplant associated coronary artery disease; 36 non-transplant associated coronary artery disease) and their donors were genotyped by polymerase chain reaction. The allele frequencies of the recipients in the transplant associated coronary artery disease and non-transplant associated coronary artery disease groups (I = 0.47 and 0.48, D = 0.53 and 0.52, respectively) did not differ significantly between the groups. However, there was a negative association between the frequency of the I allele in the donor and the development of transplant associated coronary artery disease. The D allele in the donor population of the non-transplant associated coronary artery disease group had a significantly (P < 0.01) lower frequency (0.35) than either the transplant associated coronary artery disease group (0.53) or that of the general population (0.57). Other factors analysed were recipient family history, cholesterol levels, age, sex and body mass index, donor age and acute rejection, of which the significant (P < 0.05) factors were acute rejection and sex of the recipient. CONCLUSION: These results suggest that the ACE genotype of the donor organ may be an additional risk factor for the development of coronary artery disease following cardiac transplantation and that tissue rather than circulating ACE could be implicated in the pathogenesis of this disease.

Determinants of transplant-related coronary calcium detected by ultrafast computed tomography scanning.

Coronary calcium detected by ultrafast computed tomography (CT) has been shown to be a marker of coronary artery disease in heart transplant recipients. The objective of this study was to examine the possible determinants of coronary calcium after heart transplantation. Over a 15-month period, 102 consecutive cardiac transplant recipients (mean age 53 years, 88 men) underwent ultrafast CT scanning of the heart, in addition to coronary angiography, to determine coronary calcium score on their annual follow-up (a median of 4.6 years [range 63 days to 9.1 years] after transplant). The following data were also recorded: the recipient's sex and date of birth, date of transplantation, date of ultrafast computed tomography and coronary angiography; recipient pretransplant diagnosis, history of diabetes mellitus and systemic hypertension, fasting lipid profile, immunosuppression, number of rejection episodes, and donor organ ischemic time. Forty six patients (45.1%) had total calcium scores >0 and 41 (40.2%) had at least 1 major coronary with angiographic narrowing >24%. On univariate analysis, coronary calcium was significantly associated with dyslipoproteinemia, total cholesterol was >6.0 mmol/L (240 mg/dl), triglycerides were >3.0 mmol/L (265 mg/dl), and lipoprotein(a) >30 mg/ dl; > or =25% angiographic disease was significantly associated with coronary calcium and dyslipoproteinemia. Logistic regression revealed that dyslipoproteinemia, systemic hypertension, and donor ischemic time were significant predictors of coronary calcium in transplanted hearts. We conclude that the prevalence of coronary calcium in heart transplant recipients is high and is related to recipient dyslipoproteinemia, systemic hypertension, and donor organ ischemic time.

The prognostic significance of non-invasive cardiac tests in heart transplant recipients.

The long-term mortality and morbidity of cardiac transplant recipients is related to their subsequent development of accelerated coronary atheroma and its complications. Coronary angiography was compared with non-invasive clinical assessment to see which was better in predicting clinical outcome. Ninety-one consecutive transplant recipients (mean age 53 years), in whom investigations had been performed (exercise electrocardiography, rest and exercise radionuclide ventriculography, 2-D echocardiography and coronary angiography), were followed up for a mean period of 2.1 years. Eighteen patients had 31 cardiac events. There were five cardiac-related deaths, 17 myocardial infarctions and/or onsets of heart failure, eight percutaneous transluminal coronary angioplasties and one coronary artery bypass graft. With cardiac event-free survival as the dependent variable and the results of the above investigations as independent variables, a series of univariate, bivariate and regression analyses were performed. On bivariate analysis, an echocardiographic ejection fraction of > 60% significantly predicted both survival free of myocardial infarction and/or heart failure and/or cardiac death and survival free of any cardiac event (P = 0.001 for both). Absence of coronary angiographic disease (both of < 25% and of < 50% luminal narrowing in any vessel) significantly predicted survival free of any cardiac event (P = 0.00004 and 0.015, respectively). Neither radionuclide ventriculography nor exercise electrocardiography were significant predictors of event free survival. In conclusion, echocardiography is at least as important as coronary angiography in the follow-up and prognostic assessment of cardiac transplant recipients.

Coronary artery surgery in women compared with men: analysis of coronary risk factors and in-hospital mortality in a single centre.

OBJECTIVE: To determine differences in coronary risk factors between women and men and their relation to in-hospital mortality associated with coronary artery bypass grafting. DESIGN: Prospective observational study. SETTING: A regional cardiothoracic centre. PATIENTS: 482 (362 (75%) men and 120 (25%) women) consecutive patients who had primary isolated coronary artery bypass grafting. RESULTS: The women were on average three years older than the men (63 v 60 years, P < 0.001). Women more frequently had hypertension (47% v 33%, P < 0.01), diabetes mellitus (21% v 10%, P < 0.005), hypothyroidism (9% v 2%, P < 0.003), and a family history of premature coronary heart disease (49% v 31%, P < 0.0006). More of the men were cigarette smokers (67% v 45%, P > 0.00001). Many of the women and men had dyslipidaemia. Postmenopausal women had a higher concentration of serum total cholesterol than men of a comparable age, (7.3 mmol/l v 6.5 mmol/l, P = 0.0002). Although arterial grafts were often used in both sexes, they were more often used in men than in women (91% v 78% respectively, P = 0.0003). In-hospital mortality was 2.1% (1.4% in men and 4.2% in women, P = 0.14). The estimated one year probability of survival in men who had survived 30 days was 0.99 with 95% confidence interval 0.98 to approximately 1 while that for women was 0.97 with 95% confidence interval 0.91 to approximately 1. Univariate analysis showed that preoperative history of diabetes mellitus was a predictor of mortality (P = 0.03). CONCLUSION: There were differences in the incidence and type of risk factors in men and women who had coronary artery bypass grafting. Preoperative diabetes mellitus was a predictor of in-hospital mortality.