Characteristics of serial electrocardiograms in heart transplant recipients.

To characterize "normal electrocardiogram patterns" after transplantation, serial surface 12-lead electrocardiograms (ECGs) taken 2 weeks, 1 month, and 1 year postoperatively in a group of 50 heart transplant recipients were analyzed and were correlated with clinical parameters. Some recipient atrial activity was evident in 40% of patients at 2 weeks, but in only 16% at 1 year; donor atrial activity was normal in 90% to 94% of patients at all times. ECG intervals generally were normal and did not change over time. The most prevalent abnormality was the presence of incomplete (IRBBB) or complete right bundle branch block (RBBB) patterns (14% at 2 weeks, 16% at 1 month, and 22% at 1 year). In patients with hemodynamic measurements available approximately at the time of the ECG recording 1 year following transplantation, there was a significant correlation between the presence of IRBBB and RBBB patterns and somewhat higher levels of right atrial mean pressure (6.8 versus 3.9 mm Hg, p = 0.01), pulmonary artery systolic pressure (32.5 versus 24.5 mm Hg, p = 0.001) and diastolic pressure (16.2 versus 11.2 mm Hg, p = 0.004), and right ventricular systolic pressure (31.4 versus 26.9 mm Hg, p = 0.019) and pulmonary artery wedge mean pressure (11.3 versus 7.9 mm Hg, p = 0.010). Repolarization changes were also common but decreased in frequency over time (78% at 2 weeks to 34% at 1 year) and did not correlate with the presence or absence of rejection. We conclude that ECG abnormalities in heart transplant recipients are generally mild and that IRBBB and RBBB patterns correlate with increased right heart pressures.

Progressive coronary luminal narrowing after cardiac transplantation.

Accelerated coronary disease is a major factor limiting long-term survival in cardiac transplant recipients. Coronary angiography was obtained a mean of 5.1 weeks posttransplantation and annually thereafter. Replicate projections recorded after nitroglycerine administration were quantitated using computer-assisted edge detection. Five hundred and fifteen coronary segments in 25 patients having 1-year follow-up and 353 segments in 18 patients reaching 2-year follow-up were compared with baseline angiograms. Significant change was defined as +/- 0.10 mm, equal to 3.8% change in diameter based on three standard deviations obtained from estimation of measurement error. Mean coronary diameter fell from 2.44 +/- 0.26 mm at baseline to 2.21 +/- 0.34 mm (p less than 0.001) at 1-year follow-up. This rate of diameter decline was 20-fold more rapid during the initial posttransplantation year than the rate of change of visually normal segments in nontransplant patients with coronary atherosclerosis elsewhere. There was no significant drop in mean diameter between the first and second year in those patients who had second-year studies. Decrease in absolute diameter for vessels greater than 2.9 mm significantly exceeded diameter reduction for smaller vessels but did not differ when considered as a ratio of vessel diameter. In 21 of 25 patients, mean coronary diameter reduction exceeded the three-standard deviation threshold at their last angiogram, but only two of these patients had visually detectable transplant coronary disease.

Clinical and laboratory correlates of accelerated coronary artery disease in the cardiac transplant patient.

Accelerated coronary disease in the cardiac allograft (TxCAD) is a major complication affecting long-term survival of heart transplant patients. Since the transplanted heart remains denervated, the first sign of TxCAD may be silent myocardial infarction or sudden death. The prevalence of this disease has been unaltered since the advent of cyclosporine immunosuppression. Serial annual coronary arteriograms in 132 patients undergoing transplantation after 1979 at Stanford revealed 44 patients who developed TxCAD (33%). Multiple variables, including patient lipid profile, extent of donor and recipient tissue match, age of recipient and donor, number of rejection episodes, prednisone dose, and fasting blood sugar were examined in relation to occurrence of TxCAD. Donor age was greater among the 44 patients developing TxCAD that in the 88 patients who did not develop coronary artery disease (23.5 +/- 5.8 vs 21.3 +/- 5.7 years, p less than .05). The fasting plasma triglyceride level 1 year after transplantation was 236.0 +/- 246.3 mg% in the patients with TxCAD vs 170.1 +/- 108.2 mg% in those without TxCAD (p less than .05). No other indexes, including number of rejection episodes during first posttransplant year, number of HL-A mismatches, level of maintenance steroids, fasting blood sugar, and cholesterol subfractions identified patients who developed TxCAD. We conclude that TxCAD has limited correlation with the clinical and laboratory factors analyzed. Higher donor age and elevated plasma triglycerides may be significant predisposing factors for the development of TxCAD.

A preliminary study of diltiazem in the prevention of coronary artery disease in heart-transplant recipients.

BACKGROUND: Accelerated coronary artery disease is a major cause of late morbidity and mortality among heart-transplant recipients. Because calcium-channel blockers can suppress diet-induced atherosclerosis in laboratory animals, we assessed the efficacy of diltiazem in preventing coronary artery disease in transplanted hearts. METHODS: Consecutive eligible cardiac-transplant recipients were randomly assigned to receive diltiazem (n = 52) or no calcium-channel blocker (n = 54). Coronary angiograms obtained early after cardiac transplantation and annually thereafter were used for the visual assessment of the extent of coronary artery disease. The average diameters of identical coronary artery segments were measured on the angiograms obtained at base line and at the first and second follow-up examinations. RESULTS: In the 57 patients who had all three angiograms, the average coronary artery diameter (+/- SD) 0.27 decreased in the group that received no calcium-channel blocker from 2.41 +/- 0.27 mm at base line to 2.19 +/- 0.28 mm at one year, and to 2.22 +/- 0.26 mm at two years (P < 0.001 for both years). The average diameter in the diltiazem group changed little from the base-line value of 2.32 +/- 0.22 mm (2.32 +/- 0.27 mm at one year and 2.36 +/- 0.22 mm at two years). The average change in the diameter of the segment differed significantly between the two treatment groups (P < 0.001), and the estimated effect of treatment changed only negligibly after adjustment for other relevant clinical variables. New angiographic evidence of coronary artery disease developed in 14 patients not given calcium-channel blockers, as compared with 5 diltiazem-treated patients (P = 0.082). Coronary stenoses greater than 50 percent of the luminal diameter developed in seven patients not given calcium-channel blockers, as compared with two patients given diltiazem; death due to coronary artery disease or retransplantation occurred in five patients in the group that did not receive calcium-channel blockers and none of those who received diltiazem. CONCLUSIONS: Our preliminary results suggest that diltiazem can prevent the usual reduction in the diameter of the coronary artery in cardiac-transplant recipients, but further follow-up will be required to determine whether diltiazem can decrease the long-term incidence of symptomatic coronary artery disease.

Prevalence of accelerated coronary artery disease in heart transplant survivors. Comparison of cyclosporine and azathioprine regimens.

Rapid development of diffuse, occlusive coronary artery disease in the cardiac allograft has emerged as a major limiting factor for long-term survival after transplantation. Prior multivariate analyses have failed to identify any strong predictors of this disease. We retrospectively reviewed serial annual coronary angiograms to assess the prevalence of transplant coronary artery disease. A total of 103 patients treated initially with azathioprine-based therapy were compared with a later cohort of 78 patients for whom cyclosporine was the basis of immunosuppressive therapy. The percent of patients free of angiographically visible transplant coronary artery disease at 1 year was 89% for the azathioprine group versus 86% for the cyclosporine group. At 3 years, 74% of the azathioprine group versus 63% of the cyclosporine group were free of visible disease (p = NS). By the fifth postoperative year, 58% of azathioprine-treated and 50% of cyclosporine-treated patients were free of transplant coronary artery disease (p = NS). The mean number of rejection episodes in the first year after transplantation was 2.0 for cyclosporine patients versus 2.5 for azathioprine patients. The azathioprine and cyclosporine patients were compared with respect to a variety of baseline and clinical follow-up measurements that might influence the development of coronary artery disease. Patients in the cyclosporine group had higher blood pressure (135/94 versus 123/85 mm Hg, p less than 0.001) and were receiving lower maintenance prednisone doses. This study demonstrates that improved cyclosporine immunosuppression does not decrease the time-related prevalence of transplant coronary artery disease.