The role of percutaneous transluminal coronary angioplasty in heart transplant recipients.

OBJECTIVES: Review the acute and late results of percutaneous transluminal coronary angioplasty (PTCA) in heart transplant recipients and examine the factors predictive of restenosis. BACKGROUND: Coronary graft disease (CGD) is the main factor responsible for late graft loss. Medical treatment, surgical revascularization, or retransplantation gives only suboptimal results in this regard. Therefore, PTCA has been attempted in this situation. METHODS: More than 332 heart transplantations in our institution have been performed since 1992, the date of the first PTCA in our patients. We are currently in charge of 450 patients. All the characteristics, procedure-related information, and clinical outcome of patients needing PTCA were assessed by review of each patient's clinical records. All coronary angiograms were reviewed by an independent cardiologist. RESULTS: Since 1992, 53 coronary sites have been dilated in the course of 39 procedures in 29 patients. Indication for PTCA was asymptomatic angiographic coronary graft disease in 35 sites (64.8%), angina in 9 (16.6%), silent ischemia in 2 (3.7%), acute myocardial infarction in 1 (1.8%), and CHF in 7 (12.9%). Primary success (< 50% residual stenosis) was obtained in 50 (94.3%) of 53 lesions. No periprocedural death occurred. Procedural complications were 1 transient acute renal failure and 1 persistent bleeding at the puncture site. Six months restenosis rate (defined as percent stenosis > 50%) was 32.5% (14/43). Mean follow-up was 1.27 year +/- 1.2 (SD). Five deaths (17. 2%) occurred in follow-up and were all in relation to coronary graft disease. Mean time separating PTCA from death was 0.9 year +/- 1.3 (SD). We also sought to look at factors predictive of restenosis. By multivariate analysis, a positive recipient's serology for cytomegalovirus (CMV) before the graft was the only factor found protective against restenosis (odds ratio 22.4; confidence interval 1.1 to 443.4). CONCLUSION: PTCA in heart transplant recipients allows a high level of primary success with a low periprocedural-complication rate. Restenosis rate seems equivalent to restenosis rate in native coronary arteries. Mortality during follow-up is increased in this population and is the consequence of a high level of coronary events. Recipient positivity for CMV before the graft is associated with a protective effect from restenosis.     

Long-term effect of folic acid therapy in heart transplant recipients: follow-up analysis of a randomized study

BACKGROUND: Folic acid therapy reduces homocysteine plasma levels, which seem to influence occurrence of cardiac allograft vasculopathy, but its effect on medium- or long-term prognosis after heart transplantation is unknown. METHODS: We analyzed 7-year outcome of 51 recipients randomized to receive 15 mg/day of methyltertrahydrofolate for 1 year after heart transplantation or standard therapy alone (originally, for intravascular ultrasound study of short-term cardiac allograft vasculopathy progression); recipients were observed for a further 5 to 6 years. RESULTS: Overall, 13 deaths occurred (six oncologic, five cardiovascular, two infective). Estimated 7-year survival was better in recipients randomized to folate (88%+/-6% vs. 61%+/-9%, P=0.04). After adjusting for age, pretransplant coronary artery disease, and hyperhomocysteinemia, posttransplant folic acid therapy was associated with lower mortality (relative risk [RR] 0.53, 95% confidence interval [CI] 0.25-0.97; P=0.036), apparently driven by reductions in both cancer-related and cardiovascular causes. Reduced mortality was marked in a high-risk subgroup comprising older recipients and patients transplanted because of coronary artery disease (RR 0.43, 95% CI 0.17-0.85) but not in the lower-risk subgroup (RR 1.11, 95% CI 0.22-5.61). CONCLUSIONS: Although further studies are needed, it seems reasonable to suggest folate therapy to heart transplant recipients. It is possible that properties other than homocysteine reduction may provide antitumoral benefits.     

Percutaneous coronary intervention versus medical therapy for coronary allograft vasculopathy. One center's experience.

BACKGROUND: Coronary allograft vasculopathy, a rapidly progressive form of atherosclerosis, remains the limiting factor in the long-term survival of heart transplant recipients. Some centers have attempted percutaneous coronary intervention to slow the disease process and thereby reduce mortality in these patients, but long-term follow-up data are scarce. We compared clinical outcomes in heart transplant recipients with coronary allograft vasculopathy who were treated either with percutaneous coronary intervention or with aggressive medical therapy alone. METHODS: A retrospective analysis of all heart transplant recipients at our institution who underwent surveillance coronary angiography for coronary allograft vasculopathy between 1995 and 2000 was performed. Patients with coronary allograft vasculopathy were stratified according to whether they received medical therapy or percutaneous coronary intervention. Baseline demographics, results of re-vascularization procedures and outcomes were analyzed. RESULTS: From 1995 to 2000, 301 patients underwent 602 coronary angiograms. Of the 79 patients who had angiographic evidence of coronary allograft vasculopathy, 53 were treated with aggressive medical therapy, while 26 underwent percutaneous coronary intervention in addition to aggressive medical therapy. At baseline, patients treated with aggressive medical therapy tended to be younger (54.6 +/- 13.8 years) than patients treated with percutaneous coronary intervention (62.6 +/- 7.6 years; p = 0.0079). Ejection fraction at time of diagnosis of coronary allograft vasculopathy was similar for both groups (medical therapy group, 44.4 +/- 13.4% vs percutaneous coronary intervention group, 47.2 +/- 12.7%; p = 0.38). In our cohort, heart transplant recipients with coronary allograft vasculopathy demonstrated greater mortality than heart transplant recipients without coronary allograft vasculopathy (p = 0.016). Patients who underwent percutaneous coronary intervention had a 60% re-stenosis rate at 6 months if they were treated with coronary angioplasty and an 18% re-stenosis rate if they received a coronary stent. Kaplan-Meier analysis showed no significant difference in survival in either treatment group at 1 year (80% for medical therapy group vs 95% for percutaneous coronary intervention group) or 3 years (68% for medical therapy group vs 79% for percutaneous coronary intervention group) after the angiographic diagnosis of coronary allograft vasculopathy. CONCLUSION: In this non-randomized trial, heart transplant recipients with coronary allograft vasculopathy were less likely to survive than patients without it. In addition, we found no statistical difference in mortality in heart transplant recipients with coronary allograft vasculopathy, regardless of whether they received percutaneous coronary intervention or aggressive medical therapy alone.     

Incidence, progression and functional significance of cardiac allograft vasculopathy after heart transplantation

BACKGROUND: Cardiac allograft vasculopathy after heart transplantation leads to an accelerated form of atherosclerosis with marked and often diffuse vessel wall changes that limit long-term survival. Previous studies showed contradictory results relating vessel wall changes to endothelial vasodilator response. METHODS: A total of 30 cardiac transplant recipients were studied 3, 12, and 24 months after heart transplantation. Coronary angiography was performed at rest, during supine bicycle ergometry, and after 1.6 mg sublingual nitroglycerin. Coronary cross-sectional area (biplane coronary angiography) and coronary artery wall changes (intravascular ultrasound) were assessed and extent of intimal changes correlated to vasodilator responses to nitroglycerine and bicycle ergometry. RESULTS: Intravascular ultrasound showed significant intimal thickening in 43, 64, and 58% of patients at 3, 12, and 24 months. Intimal thickening 3 months after transplantation was related to donor age (r=0.70, P<0.01) but did not predict progression of disease that manifested itself angiographically as a decrease in coronary cross-sectional area at 12 and 24 months (P<0.005) and significant coronary stenosis in 12% of patients after 24 months. Endothelium-independent vasodilatation after nitroglycerin (33+/-15, 44+/-20, and 43+/-24%) was normal. Endothelium-dependent, flow-induced vasodilatation during exercise was decreased (14+/-11, 18+/-14, and 16+/-17%) but did not correlate to intimal changes assessed by ultrasound. CONCLUSIONS: The study confirms the high incidence of intimal thickening after heart transplantation as assessed by intravascular ultrasound. Impaired exercise-induced vasodilatation suggests diminished bioavailability of endothelium-derived nitric oxide to physiological stimulation but the lack of relationship between coronary wall changes and this functional impairment suggests intermittent and presumably reversible endothelial injury in graft atherosclerosis.     

The influence of donor gender on allograft vasculopathy: evidence from intravascular ultrasound

BACKGROUND: Allograft vasculopathy is a major risk factor for mortality following cardiac transplantation. Several immune and nonimmune factors have been evaluated as risk factors for the development of coronary vasculopathy. OBJECTIVE: We evaluated the influence of donor gender on the progression of coronary vasculopathy in heart transplant recipients. METHODS: Eighty-nine heart transplant recipients (67 men, 22 women of mean age: 56 +/- 12 years) underwent serial volumetric intravascular ultrasound analysis (IVUS) at baseline (within 1 month) and at 1 year after transplantation. Patients were divided into four groups in relation to the donor-recipient gender status: female-female, n=17; female-male, n=28; male-female, n=5; male-male, n=39. Ultrasound images were recorded during an automated pullback and with an equal number of slices (average=22 per coronary vessel). The measured IVUS indices for the left anterior descending artery were: change in maximal intimal thickness, average intimal area, total plaque volume, and intimal index. RESULTS: Patients were similar in baseline characteristics. At 1 year after transplantation, IVUS indices of coronary vasculopathy were significantly increased among recipients of female allografts (P <.05). CONCLUSION: Heart transplant recipients of female allografts display increased coronary vasculopathy progression.     

Early alterations of myocardial blood flow reserve in heart transplant recipients with angiographically normal coronary arteries.

BACKGROUND: The evaluation of the coronary reserve provides valuable information on the status of coronary vessels. Therefore, we studied with positron emission tomography (PET) and 13N-ammonia the myocardial blood flow (MBF) reserve in heart transplant recipients free of allograft rejection and with angiographically normal coronary arteries early after heart transplantation (HTx). The MBF reserve was calculated as the ratio between MBF after dipyridamole injection and basal MBF normalized for the rate-pressure product. METHODS: Patients were studied within 3 months (group A, n = 12) or more than 9 months (group B, n = 12) after HTx. Five patients have been studied both during the early and late period after HTx. Results were compared to those obtained in 7 normal volunteers (NL). RESULTS: Group A recipients had a significantly lower dipyridamole MBF (in ml/min/100 gr of tissue) than that of group B recipients (142+/-34 vs 195+/-59, p<0.05). This resulted in a significant decrease in MBF reserve early after HTx (group A: 1.82+/- 0.33) and a restoration to normal values thereafter (group B: 2.52+/- 0.53 vs NL: 2.62+/-0.51, p = ns). Separate analysis of 5 patients studied twice is consistent with these results. CONCLUSION: This study shows that in heart transplant recipients free of allograft rejection and with normal coronary angiography, MBF reserve is impaired early after HTx. Restoration within one year suggests that this abnormality does not represent an early stage of cardiac allograft vasculopathy.     

Three-year results of a randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant recipients.

BACKGROUND: This study reports the 36-month results of a randomized, double-blind, active-controlled trial of mycophenolate mofetil (MMF) vs azathioprine (AZA) in heart transplant patients. METHODS: Patients were randomized at the time of transplant to receive MMF (1,500 mg twice a day, N = 327) or AZA (1.5 to 3 mg/kg in 4 daily doses, N = 323) in addition to cyclosporine and corticosteroids; 289 patients in each group received study drug. Data were analyzed in all randomized patients (enrolled) and in patients who received study medications (treated). Clinical and graft assessments continued for 36 months. RESULTS: For the co-primary end-point, 53 of 289 (18.3%) AZA-treated patients either died or received another transplant compared with 34 of 289 (11.8%) MMF-treated patients (p < 0.01). Time to re-transplantation or patient death was significantly shorter for AZA- than MMF-treated patients (p = 0.029). In patients undergoing intravascular ultrasound, the change in mean maximal intimal thickness was less for the MMF group than for the AZA group (0.06 +/- 0.03 mm vs 0.13 +/- 0.03 mm, respectively; p = 0.056). No significant differences between treatments were observed in quantitative coronary angiographic measurements of transplant coronary vasculopathy. Congestive heart failure, atrial arrhythmia and leukopenia were more common in the AZA group, whereas diarrhea, esophagitis, Herpes simplex, Herpes zoster and cytomegalovirus (CMV) tissue invasion were more common in MMF-treated patients. CONCLUSION: MMF reduces mortality and graft loss up to 36 months after transplantation.     

Outcome of hearts with cold ischemic time greater than 300 minutes. A case-matched study.

OBJECTIVE: Expansion of potential donor pool may be facilitated by using cardiac allografts with long ischemic time. Early graft failure and potential relation to transplant coronary artery disease remains a concern. We sought to evaluate outcomes of heart transplantation in recipients of donor allografts with prolonged ischemia time. METHODS: The study group consisted of 46 (mean age, 52 years) consecutive patients at UCLA from 1994 to 2002 that underwent heart transplantation with ischemia time > 300 min. This group was compared to a case-matched control group of 46 (mean age, 51 years) patients identified from our database during this time frame for the following factors: UNOS status, congenital heart disease diagnosis, preop inotropes, pretransplantation creatinine > 1.5 and recipient age. Primary endpoint was mortality and secondary were rejection rate and transplant coronary artery disease. Allografts were perfused and stored in cold University of Wisconsin solution. RESULTS: Mean donor ages of the study and case-matched control group were 34+/-15 and 34+/-14 years, respectively. Mean ischemia times were 388 (range, 301-600 min) and 173 (range, 96-236 min), respectively. The death incidence rate per 100 transplants per year was 9% for the study group and 7.4% for the matched group (P = 0.50). Thirty-day mortality for the study and case-matched groups were 4.3 and 2.1%, respectively (P = 0.9). Late mortality was 16.5 and 18.5%, respectively (P = 0.9). The risk of death after 30 days was 7.5 and 5.8%, respectively (P = 0.5, log-rank). One-year incidence of acute cellular rejection in the study and case-matched groups were 2 and 4.5% (P = 0.36), respectively. One-year incidence of transplant coronary artery disease in the study and case-matched groups were 4.3 and 5.4%, respectively (P = 0.68). CONCLUSIONS: Donor hearts with ischemia time greater than 300 min provide comparable early and intermediate outcomes given judicious and careful donor and recipient matching and our current techniques of myocardial preservation and modified reperfusion.     

Left ventricular assist devices as bridge to heart transplantation: The Niguarda Experience

BACKGROUND: Congestive heart failure is the leading cause of death in Western countries. Heart transplantation currently is the only accepted therapy for patients with end-stage heart failure, but the supply of donor hearts is inadequate, and different mechanical circulatory support systems have been investigated as bridges to heart transplant. METHODS: Since April 1992, 53 patients (47 men, 6 women, aged 12 to 61 years) received left ventricle mechanical circulatory support as bridge to heart transplant. The two principal devices used were: the Novacor LVAS in 31 patients and the DeBakey VAD in 11 patients. RESULTS: All patients survived the operation. Mean duration of LVAD support was 2.8 +/- 5.6 months. Thirty-seven patients (71.1%) underwent heart transplantation. Twelve major bleeding episodes occurred in nine patients (16.9%). Globally, major and minor neurologic events occurred in 13 patients (24.5%). Ten patients (19.9%) assisted with the Novacor Wearable LVAS device were discharged at home while waiting for heart transplant (HTx). The mean follow-up of the 34 discharged transplanted patients was 45.3 +/- 37 months. Actuarial survival of transplanted patients while on LVAD was 91.0 +/- 4.9% and 83.4 +/- 8.5% at 1 and 5 years, respectively. No differences in post-transplant long-term survival and rejection and allograft vasculopathy occurred between patients transplanted with or without LVAD implanted. CONCLUSIONS: LVAD therapy proved to be effective in bridging patients with end-stage heart failure to HTx. While on LVAD support, patients assisted with implantable wearable devices could be discharged at home, ameliorating their quality of life. The excellent survival rate after HTx is concomitant with a low incidence of rejection and cardiac allograft vasculopathy.     

Comparison of long-term results of drug-eluting stent and bare metal stent implantation in heart transplant recipients with coronary artery disease

The aim of the study was to compare long-term results of intracoronary implantation of drug-eluting stents (DES) and bare metal stents (BMS) in patients suffering from transplant coronary artery disease (TxCAD). MATERIAL AND METHODS: We performed a retrospective analysis of all intracoronary stent implantations for TxCAD among subjects with at least one follow-up coronary angiography. We identified 28 sirolimus-eluting DES (n = 17) patients, 24 BMS (n = 13 patients), and both DES and BMS (n = 7 patients) implantations among 23 recipients. Mean follow-up after DES was 14 months and after BMS implantation, 20 months. We compared the occurrence of in-stent restenosis (ISR), and patient survival in the context of risk factors that were identified separately for each stent type. Significance was assessed using the log-rank, chi(2) and Mann-Whitney U test. RESULTS: There were 2 (7%) ISR among DES versus 14 (58%) ISR among BMS (P = .0002) patients, with a longer time of freedom from IRS after DES implantation (P = .022). There were three deaths (18%) among DES, four (31%) with BMS, and one (14%) with DES and BMS (P = NS). Left anterior descending artery was the place of DES implantation in 17 (61%) versus 10 (42%) of BMS cases (P = NS). Risk factor profile was comparable except for a higher age at the time of transplantation (46 +/- 7 vs 41 +/- 6 years; P = .011) and stent implantation (54 +/- 7 vs 49 +/- 6 years; P = .0002) for DES. CONCLUSION: Favorable long-term results of sirolimus-eluting stents over BMS implanted for TxCAD suggested their preferential use in heart transplant recipients.     

Symptomatic acute myocardial infarction in a cardiac transplant recipient successfully treated with primary coronary angioplasty: evidence of prognostic importance of chest pain after cardiac transplantation.

Accelerated coronary artery disease remains the limiting factor in the long-term survival of heart transplant (HT) recipients and occurs in approximately 50% of patients by 5 years after transplantation. Sequelae of graft arteriosclerosis include congestive heart failure (due to acute or chronic ischemia), graft loss, and death. Unfortunately, as a consequence of cardiac denervation, symptoms are often atypical or completely absent, and thus presentation with an acute coronary syndrome is extremely uncommon. We describe the case of an HT recipient with a typical clinical picture of an acute myocardial infarction (MI), who presented to our hospital 2 hours after the onset of symptoms and was successfully treated with primary percutaneous transluminal coronary angioplasty (PTCA).     

The outcome of heart transplantation in hepatitis C-positive recipients

Background

Clinical outcomes of heart transplantation (HTx) among recipients with chronic hepatitis C virus (HCV) infection are poorly understood especially in Asia. Therefore, this study evaluated these clinical outcomes.

Methods

Using retrospective chart review we collected data on 385 patients including 20 HCV-positive recipients at the time of transplantation. We obtained information on demographics features, serial transaminases, graft function, patient survival as well as the incidences of acute hepatitis and transplant coronary artery disease.

Results

Between 1987 and 2010, the 20 HCV-positive patients had a median age at transplantation of 52 years (range, 30-63). Seventeen were men and three women. All the patients were classified as Child-Pugh class A; two had cirrhosis prior to HTx. Over a mean follow-up of 63 months (range, 2 days to 187 months), there were 11 deaths, including two hospital mortalities and nine subsequent deaths. Only one mortality (5%) was related to Child-Pugh class C cirrhosis, despite liver transplantation. Among the other 19 deceased or surviving recipients, there was no evidence of hepatic dysfunction or hepatocellular carcinoma. Transplant coronary artery disease was detected in six patients (30%). There was no significant difference in Kaplan-Meier actuarial survival between the HCV-positive and HCV-negative recipients (P = .59).

Conclusions

There was no significant difference in patient survival or graft function between HCV-positive and HCV-negative HTx recipients. Additionally, HCV-positive recipients were not at an increased risk of hepatic failure or accelerated transplant coronary artery disease.     

Clinical implications of late mitral valve regurgitation appearance in the follow-up of heart transplantation

BACKGROUND: Tricuspid regurgitation is frequently observed after orthotopic heart transplantation (OHT), in association with severe pulmonary hypertension. However, the incidence of left-sided valvular disease has not been addressed. AIM: We analyzed the incidence and prognostic implications of left-sided valve disease in 141 patients after OHT. METHODS: Echocardiography was performed with every endomyocardial biopsy during the first year after OHT and every 6 months thereafter. Mitral regurgitation (MR) grade II or III was considered significant. Graft vasculopathy was assessed using coronary angiography. RESULTS: Eight patients (6%) developed significant left-sided valvular disease, namely, MR in 6 (4%) and aortic regurgitation (AR) in 2 (1.4%). The 2 cases with AR were diagnosed the first week after OHT, whereas significant MR was diagnosed at mean follow- up of 34 +/- 6 months. Mean regurgitant orifice and volume were 34 +/- 14 mm2 and 41 +/- 15 mL/beat, respectively. Patients with significant MR had experienced a greater number of acute rejection episodes >or=3A, (1.8 +/- 1.7 vs 0.8 +/- 1.05; P = .02) and were associated with allograft vasculopathy in 83% vs 6% among unaffected patients (P = .0001). Four of 6 patients with significant MR died during follow-up (67%) and 1 of the living patients underwent reparative mitral valve surgery. The probability of survival using Kaplan-Meier curves was significantly lower when patients developed late significant MR (54% vs 76%; P = .0001). CONCLUSIONS: The incidence of significant left-sided valvular disease after OHT was low. MR was associated with a higher degree of previous acute rejection, of graft vasculopathy, and mortality. The presence of moderate or severe MR of late appearance identified a group of OHT patients with poor outcomes.     

Computerized scoring of histopathology for predicting coronary vasculopathy, validated by intravascular ultrasound.

BACKGROUND: Allograft coronary vasculopathy results from a complex interplay between immunologic and non-immunologic factors. We devised a computerized biopsy scoring method based on histopathology to predict the development of coronary vasculopathy. METHODS: One hundred forty heart transplant recipients underwent serial intravascular ultrasound analysis at baseline (within 1 month) and at 1 year after transplantation and were evaluated for development of coronary vasculopathy (change in coronary maximal intimal thickness, CMIT). We evaluated serial endomyocardial biopsy specimens for cellular rejection, vascular rejection, ischemia, and fibrosis. In a mathematical model, we computed a biopsy score in each patient based on the duration and severity of histopathology. RESULTS: We found a significant correlation between biopsy score (RY) and progression of coronary vasculopathy (r = 0.54, p = 0.001). Using a sensitivity analysis method, an RY value of > or =560 predicted development of coronary vasculopathy with a sensitivity of 86%, specificity of 62%, and diagnostic accuracy of 80%. Compared with patients with low-risk biopsy scores (RY < 560, n = 37), patients with high-risk biopsy scores (RY > or = 560, n = 103) had increased progression of coronary vasculopathy (CMIT, 0.59 +/- 0.29 vs 0.19 +/- 0.10 mm, p < 0.001) and worse 7-year event-free survival (60% vs 91%, p = 0.01). CONCLUSION: The biopsy score is an effective method for predicting the development of coronary vasculopathy and for predicting outcome in cardiac transplant recipients.     

Functional and morphological findings in heart transplant recipients with a normal coronary angiogram: an analysis by dobutamine stress echocardiography, intracoronary Doppler and intravascular ultrasound.

BACKGROUND: Coronary angiography is still the routine screening method for cardiac allograft vasculopathy in most transplant centers. This study was designed to analyze functional and morphologic changes in heart transplant recipients with normal angiographic findings. METHODS: Dobutamine stress echocardiography and intracoronary ultrasound were obtained in 56 patients with a normal coronary angiogram 41+/-31 months after heart transplantation. Intracoronary Doppler flow velocity measurements before and after intracoronary adenosine administration were performed in 34 of 56 patients. Any regional wall motion abnormalities detected by stress echocardiography were regarded as abnormal. By quantitative intracoronary ultrasound analysis using a 6-grade scale, a mean grade of all coronary segments >3.0 was defined as significant intimal hyperplasia. RESULTS: Only 17 patients (30%) showed both a normal dobutamine stress echocardiogram and absence of significant intimal hyperplasia by intravascularultrasound. Abnormal findings were observed in 39 patients (70%): both by dobutamine stress echocardiography and intravascular ultrasound in 22 patients, by intravascular ultrasound alone in 11 patients, and by dobutamine stress echocardiography alone in 6 patients. Coronary flow velocity reserve did not discriminate between patients with normal or abnormal intravascular ultrasound or dobutamine stress echocardiographic findings. Conclusions: Only a minority of heart transplant patients with a normal coronary angiogram is free of pathological changes, when assessed by intravascular ultrasound and dobutamine stress echocardiography. Coronary flow velocity reserve does not seem useful to further characterize these patients.     

Heart-lung versus double-lung transplantation for suppurative lung disease

OBJECTIVE: The purpose of this study was to compare outcomes after heart-lung or double-lung transplantation in patients undergoing transplantation because of end-stage suppurative lung disease. METHODS: We reviewed our experience in patients with cystic fibrosis or bronchiectasis who had heart-lung or double-lung transplantation between January 1988 and September 1997. Twenty-three patients (14 male, 21 cystic fibrosis) had heart-lung transplantation and 24 patients (8 male, 19 cystic fibrosis) had double-lung transplantation. There were no statistically significant differences between the groups in age, weight, preoperative creatinine level, cytomegalovirus status, maintenance immunosuppression, or donor demographics. Patients received induction therapy with monoclonal (OKT3) or polyclonal (rabbit anti-thymocyte globulin) antibody. RESULTS: Sixteen of 24 patients had double-lung transplantation after 1994 whereas 13 of 22 patients had heart-lung transplantation before 1991, allowing longer follow-up for the heart-lung group. Mean waiting times for transplantation were 270 +/- 245 days (heart-lung) and 361 +/- 229 days (double-lung; P =.20). The 1-, 3-, and 5-year actuarial survival figures were respectively 86%, 82%, and 65% (heart-lung) and 96%, 75%, and unavailable (double-lung; P = no significant difference). The 1-, 3-, and 5-year rates of freedom from obliterative bronchiolitis were respectively 77%, 61%, and 45% (heart-lung) and 86%, 78%, and unavailable (double-lung; P = no significant difference). Linearized overall infection rates (events/100 patient-days) were 2.05 +/- 0.33 (heart-lung) and 2.34 +/- 0.34 (double-lung; P = NS) at 3 months. Thirty-day survival was 100% (heart-lung) and 96% (double-lung). There were 7 late deaths among heart-lung recipients (3 obliterative bronchiolitis, 2 infection, 0 graft coronary artery disease, 2 other) whereas 2 late deaths related to obliterative bronchiolitis occurred in double-lung recipients. Graft coronary artery disease (all stenoses < 50%) affected 15% of heart-lung survivors, whereas 3 double-lung recipients (12.5%) required either bronchial dilatation or stenting. CONCLUSION: Heart-lung and double-lung transplantation provide similar palliation for patients with end-stage suppurative lung disease. Therefore double-lung transplantation should be the preferred operation for most patients with end-stage suppurative lung disease.     

Efficacy and safety of atorvastatin after pediatric heart transplantation.

BACKGROUND: Lipid abnormalities are prevalent after pediatric and adult heart transplantation. 3-Hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase inhibitors are efficacious and safe and can lower the incidence of graft coronary artery disease after heart transplantation in adults. Given the high prevalence of lipid abnormalities and the increased recognition of graft coronary disease in children, we retrospectively investigated the efficacy and safety of atorvastatin among pediatric heart transplant recipients. METHODS: Thirty-eight patients were started on atorvastatin 48.2 +/- 54.4 months after transplantation. Atorvastatin dosage was 0.2 +/- 0.1 mg/kg per day. No patient had changes in drug dose unless there was evidence for rhabdomyolysis, myositis or an asymptomatic rise in creatine kinase above normal. Laboratory studies included total cholesterol, triglycerides; high, low and very low-density lipoproteins (HDL, LDL and VLDL, respectively); creatine kinase; creatine; and serum alanine transaminase. RESULTS: Significant declines in total cholesterol (20%), triglyceride (18%) and LDL (26%) were observed after starting atorvastatin therapy. There were no significant changes in HDL or VLDL compared with baseline. There were also no differences in alanine transaminase pre- vs post-atorvastatin therapy. Complications included muscle pain (n = 2) and asymptomatic elevations in creatine kinase (n = 2). Two of these 4 patients developed rhabdomyolysis. Excluding these 4 patients, creatine kinase did not rise compared with baseline. No patient developed alterations in renal function. CONCLUSIONS: Use of atorvastatin in pediatric heart transplant recipients is effective in lowering total cholesterol, triglyceride and LDL without altering HDL levels. Complications included rhabdomyolysis, seen in 5%. Baseline and routine screening of creatine kinase should be employed in all pediatric patients undergoing HMG-CoA reductase inhibitor therapy.     

Smoking After Cardiac Transplantation

Although smoking cessation is a prerequisite prior to listing for cardiac transplantation, some patients return to smoking after recovery. We have covertly assessed the smoking habits of our cardiac transplant recipients (with ethical approval) since 1993 by measuring urinary cotinine: a level of >500 ng/mL signifying continued tobacco use. We retrospectively analyzed survival, causes of death and the development of graft coronary artery disease (GCAD) with respect to the number of positive and negative cotinine levels. One hundred four of 380 (27.4%) patients tested positive for active smoking at some point posttransplant, and 57 (15.0%) tested positive repeatedly. Smokers suffered significantly more deaths due to GCAD (21.2% vs. 12.3%, p < 0.05), and due to malignancy (16.3% vs. 5.8%, p < 0.001). In univariate analysis, smoking after heart transplantation shortened median survival from 16.28 years to 11.89 years. After correcting for the effects of pretransplant smoking in time-dependent multivariate analysis, posttransplant smoking remained the most significant determinant of overall mortality (p < 0.00001). We conclude that tobacco smoking after cardiac transplantation significantly impacts survival by accelerating the development of graft vasculopathy and malignancy. We hope that this information will deter cardiac transplant recipients from relapsing, and intensify efforts in improving cessation rates.     

Predictors of reduced coronary flow reserve in heart transplant recipients without angiographically significant coronary artery disease

BACKGROUND: Determination of coronary flow reserve (CFR) is increasingly used to assess the functional significance of cardiac allograft vasculopathy. Although the relation between CFR and angiographically defined vasculopathy has been studied extensively, little is known about other factors determining CFR in heart transplant recipients without significant lesions by coronary angiography. METHODS: Sixty consecutive patients were studied 0.5 to 148 months after heart transplantation with intracoronary Doppler and intravascular ultrasound. An endothelium-independent CFR< or =2.5 was defined as abnormal. Stepwise logistic regression analysis was used to identify factors (demographic data of donor and recipient, lipid profile, epicardial vessel morphology by intravascular ultrasound, left ventricular hypertrophy, acute rejection episodes, and hemodynamics) potentially associated with a reduced CFR. RESULTS: Only the presence of left ventricular hypertrophy (48% vs. 14%, P=0.007 and P=0.023, bivariate and multivariate analysis, respectively) and higher donor ages (41+/-12 vs. 29+/-11 years, P=0.002 and P=0.013, bivariate and multivariate analysis, respectively) showed an independent association with an abnormal flow reserve. CFR in patients with left ventricular hypertrophy was reduced due to higher baseline flow velocities (27+/-11 vs. 20+/-6 cm/sec, P=0.004). Furthermore, resting flow velocity increased as a function of donor age (r=0.264, P=0.047), while hyperemic flow velocity was not different. Other patient characteristics and hemodynamics did not affect CFR. CONCLUSION: The presence of left ventricular hypertrophy and higher donor ages independently contribute to a reduced CFR in patients after heart transplantation. This reduction in CFR is due to elevated baseline flow velocities rather than to a change in hyperemic flow velocities. These findings should be taken into account for the interpretation of reduced CFR values obtained by intracoronary Doppler in heart transplant recipients without angiographically overt coronary lesions.