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BackgroundThe belief that vascular remodeling and intimal hyperplasia are causes of luminal narrowing in cardiac allograft vasculopathy (CAV) is controversial. This study evaluated the relationship of vascular remodeling and intimal hyperplasia to luminal narrowing 1 year after orthotopic heart transplantation.MethodsIntravascular ultrasound imaging was performed on 190 cardiac transplant recipients at baseline and again 1 year after transplantation as part of a randomized trial of mycophenolate mofetil (MMF) and azathioprine (Aza). Studies 1 year apart were matched at 625 sites. All sites were classified into positive, non-significant and negative remodeling patterns, depending on a change of +/-10% in external elastic membrane area. Of the 190 patients, 99 were randomized to receive MMF, and 91 to receive Aza.ResultsA total of 625 sites were observed. Of these, 52% had no remodeling, 25% exhibited vessel dilation, and 23% had vessel shrinkage in the presence of variable intimal growth (Delta intimal area: 0.73 +/- 1.70 mm2, p < 0.0001; 1.23 +/- 2.02 mm2, p < 0.0001; and 0.20 +/- 1.40 mm2, p = 0.09, respectively). Sixty percent of the lumen loss was due to a decrease in external elastic membrane area and 40% to an increase in intimal area (p = 0.005). Compared with Aza-treated patients, the MMF-treated patients had a lower incidence of vessel shrinkage (17% vs 28%, p = 0.001), and a trend for smaller maximum intimal thickness (0.21 +/- 0.25 mm vs 0.29 +/- 0.31 mm, p = 0.052).ConclusionsPositive remodeling is associated with intimal growth, but negative remodeling does not correlate with any specific change in intimal hyperplasia. Constrictive remodeling is more responsible than intimal hyperplasia for the luminal narrowing that occurs. MMF is more efficacious than azathioprine in preventing the development of CAV at 1 year, by reducing the degree and incidence of vessel shrinkage and the progression of intimal hyperplasia.

We evaluated the short-term safety and efficacy of using the TandemHeart(R) percutaneous ventricular assist device in high-risk patients undergoing aortic valvuloplasty procedures. Aortic valvuloplasty was performed in 4 patients who had no ventricular assist device support and in 7 patients who used the TandemHeart for hemodynamic support. The age range was 65 to 94 years (mean, 83 +/- 11 yr). The mean ejection fraction was 0.30 +/- 0.14. A transseptal antegrade approach to the aortic valve was used in 8 patients and a retrograde approach in the remaining 3. WITH THE TANDEMHEART, ALL PROCEDURES WERE TECHNICALLY SUCCESSFUL: each patient survived at least 1 month after the procedure. The mean total balloon inflation time was 37 +/- 10 sec. The aortic valve area was 0.6 +/- 0.1 cm(2) before the procedure and 0.9 +/- 0.2 cm(2) afterwards (P=0.006). Without TandemHeart support, 1 patient died of cardiac arrest during the procedure. The mean total balloon inflation time was 11 +/- 3 sec. Aortic valve area was 0.6 +/- 0 cm(2) before the procedure and 1.1 +/- 0.3 cm(2) afterwards (P=0.3). No patient developed aortic regurgitation. We conclude that use of the TandemHeart for hemodynamic support during high-risk aortic valvuloplasty is associated with favorable intraprocedural and short-term outcomes. With the TandemHeart in place, balloon placement was precise, and inflation was maintained for up to 45 sec without balloon displacement. These attributes are essential during stent-valve placement, are achieved without rapid ventricular pacing, and may reduce the risk of global ischemia and death.

AimsTo assess the time-course of intimal hyperplasia and vascular remodelling, and their relative contributions on luminal narrowing in transplant coronary artery disease (TCAD) by a 3-year serial intravascular ultrasound (IVUS) study.Methods and resultsSerial IVUS examinations were performed in 90 cardiac transplant recipients at 1.4+/-0.6 months after transplantation and again annually thereafter for 3 years. From 90 arteries, 304 sites were matched from baseline to the third year post-transplant. Based on the change in external elastic membrane (EEM) area +/-10% at 1 year, 304 sites were divided into three groups: sites with no remodelling (52%); early constrictive remodelling (26%); and early compensatory enlargement (22%). Greater intimal growth was seen at 1 year in sites with early compensatory enlargement, whereas there was no change in intimal area in sites with early constrictive remodelling. Over 3 years, the cumulative lumen loss was greater in sites with early constrictive remodelling than in sites with early compensatory enlargement or no remodelling (P

ObjectivesThis study sought to evaluate the influence of donor lesions on the development of cardiac allograft vasculopathy and outcomes in heart transplant recipients.BackgroundAfter 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.MethodsIntravascular 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.ResultsDonor 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).ConclusionsPre-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.

UnlabelledThe mycophenolate mofetil (MMF) trial involved 650 heart transplant patients from 28 centers who received MMF or azathioprine (AZA), both in combination with cyclosporine and corticosteroids. Baseline and 1-year intravascular ultrasound (IVUS) were performed in 196 patients (102 MMF and 94 AZA) with no differences between groups in IVUS results analyzed by morphometric analysis (average of 10 evenly spaced sites, without matching sites between studies). Baseline to first-year IVUS data can also be analyzed by site-to-site analysis (matching sites between studies), which has been reported to be more clinically relevant. Therefore, we used site-to-site analysis to reanalyze the multicenter MMF IVUS data.ResultsIVUS images were reviewed and interpretable in 190 patients (99 MMF and 91 AZA) from the multicenter randomized trial. The AZA group compared to the MMF group had a larger number of patients with first-year maximal intimal thickness (MIT)>or=0.3 mm (43% vs. 23%, p=0.005), a greater decrease in the mean lumen area (p=0.02) and a decrease in the mean vessel area (the area actually increased in the MMF group, p=0.03).ConclusionMMF-treated heart transplant patients compared to AZA-treated patients, both concurrently on cyclosporine and corticosteroids, in this study have significantly less progression of first-year intimal thickening.

BackgroundIt is unclear to what extent the "Glagov phenomenon" occurs in transplant coronary artery disease (TCAD). The objective of this study was to evaluate the relationship between intimal hyperplasia and compensatory enlargement in TCAD.MethodsIntravascular ultrasound imaging was performed on 190 cardiac transplant recipients at (1.4 +/- 0.6) months and again (12.1 +/- 0.7) months after cardiac transplantation. Studies 1 year apart were matched at 625 sites. There were 345 coronary artery sites that had an increase in intimal area > 10% from baseline to one year, and this comprised the data set of the present study.ResultsAt the first year, 91% of coronary artery sites with intimal growth had a total cross-sectional area stenosis < or = 40%, but 38% of the sites showed a decrease of > 10% in lumen area. Receiver operating characteristic curve demonstrated that the change in cross-sectional area stenosis cut-off level at year 1 was 8% with a sensitivity of 75% and a specificity of 82% in predicting lumen loss. At a total cross-sectional area stenosis of 20%, sensitivity was 65% with a specificity of 81% in predicting lumen loss.ConclusionsIn TCAD, vessel enlargement as a compensatory mechanism for plaque growth is generally inadequate. Instead of continued vessel expansion, luminal narrowing develops when there is more than 8% cross-sectional area filled with intimal hyperplasia. In distinction to native coronary artery atherosclerotic disease, the transition point in transplant vasculopathy where the lumen is diminished by increasing intimal growth, occurs at a lower threshold, 20% vs 40% of vessel cross-sectional area.

Late morbidity and death as a result of progressive coronary vascular obliteration remains a major unsolved problem after orthotopic heart transplantation. Various percutaneous catheter intervention (PCI) methods have been used to treat transplant coronary artery disease (CAD), but few reports have assessed the longitudinal results of these procedures. Of 1,440 cardiac transplant patients at University of California, Los Angeles, Medical Center, treated between 1984 and 2004, 65 patients who had undergone orthotopic heart transplantation underwent PCI on a total of 156 coronary artery lesions because of transplant CAD between July 1993 and August 2004. The procedural success rate was 93%. Angiographic follow-up was available for 42 patients and 101 lesions 9.5 +/- 5.8 months after PCI. The global restenosis rate was 36%. Multivariate analysis was used to assess 49 clinical, angiographic, and immunologic variables per lesion. The use of a cutting balloon increased the risk of restenosis (odds ratio 11.5, p