Multicenter Analysis of Immune Biomarkers and Heart Transplant Outcomes: Results of the Clinical Trials in Organ Transplantation-05 Study.

Identification of biomarkers that assess posttransplant risk is needed to improve long-term outcomes following heart transplantation. The Clinical Trials in Organ Transplantation (CTOT)-05 protocol was an observational, multicenter, cohort study of 200 heart transplant recipients followed for the first posttransplant year. The primary endpoint was a composite of death, graft loss/retransplantation, biopsy-proven acute rejection (BPAR), and cardiac allograft vasculopathy (CAV) as defined by intravascular ultrasound (IVUS). We serially measured anti-HLA- and auto-antibodies, angiogenic proteins, peripheral blood allo-reactivity, and peripheral blood gene expression patterns. We correlated assay results and clinical characteristics with the composite endpoint and its components. The composite endpoint was associated with older donor allografts (p < 0.03) and with recipient anti-HLA antibody (p < 0.04). Recipient CMV-negativity (regardless of donor status) was associated with BPAR (p < 0.001), and increases in plasma vascular endothelial growth factor-C (OR 20; 95%CI:1.9-218) combined with decreases in endothelin-1 (OR 0.14; 95%CI:0.02-0.97) associated with CAV. The remaining biomarkers showed no relationships with the study endpoints. While suboptimal endpoint definitions and lower than anticipated event rates were identified as potential study limitations, the results of this multicenter study do not yet support routine use of the selected assays as noninvasive approaches to detect BPAR and/or CAV following heart transplantation.

Everolimus versus mycophenolate mofetil in heart transplantation: a randomized, multicenter trial.

In an open-label, 24-month trial, 721 de novo heart transplant recipients were randomized to everolimus 1.5 mg or 3.0 mg with reduced-dose cyclosporine, or mycophenolate mofetil (MMF) 3 g/day with standard-dose cyclosporine (plus corticosteroids ± induction). Primary efficacy endpoint was the 12-month composite incidence of biopsy-proven acute rejection, acute rejection associated with hemodynamic compromise, graft loss/retransplant, death or loss to follow-up. Everolimus 1.5 mg was noninferior to MMF for this endpoint at month 12 (35.1% vs. 33.6%; difference 1.5% [97.5% CI: -7.5%, 10.6%]) and month 24. Mortality to month 3 was higher with everolimus 1.5 mg versus MMF in patients receiving rabbit antithymocyte globulin (rATG) induction, mainly due to infection, but 24-month mortality was similar (everolimus 1.5 mg 10.6% [30/282], MMF 9.2% [25/271]). Everolimus 3.0 mg was terminated prematurely due to higher mortality. The mean (SD) 12-month increase in maximal intimal thickness was 0.03 (0.05) mm with everolimus 1.5 mg versus 0.07 (0.11) mm with MMF (p < 0.001). Everolimus 1.5 mg was inferior to MMF for renal function but comparable in patients achieving predefined reduced cyclosporine trough concentrations. Nonfatal serious adverse events were more frequent with everolimus 1.5 mg versus MMF. Everolimus 1.5 mg with reduced-dose cyclosporine offers similar efficacy to MMF with standard-dose cyclosporine and reduces intimal proliferation at 12 months in de novo heart transplant recipients.

Effect of nesiritide in patients with acute decompensated heart failure.

BACKGROUND: Nesiritide is approved in the United States for early relief of dyspnea in patients with acute heart failure. Previous meta-analyses have raised questions regarding renal toxicity and the mortality associated with this agent. METHODS: We randomly assigned 7141 patients who were hospitalized with acute heart failure to receive either nesiritide or placebo for 24 to 168 hours in addition to standard care. Coprimary end points were the change in dyspnea at 6 and 24 hours, as measured on a 7-point Likert scale, and the composite end point of rehospitalization for heart failure or death within 30 days. RESULTS: Patients randomly assigned to nesiritide, as compared with those assigned to placebo, more frequently reported markedly or moderately improved dyspnea at 6 hours (44.5% vs. 42.1%, P=0.03) and 24 hours (68.2% vs. 66.1%, P=0.007), but the prespecified level for significance (P≤0.005 for both assessments or P≤0.0025 for either) was not met. The rate of rehospitalization for heart failure or death from any cause within 30 days was 9.4% in the nesiritide group versus 10.1% in the placebo group (absolute difference, -0.7 percentage points; 95% confidence interval [CI], -2.1 to 0.7; P=0.31). There were no significant differences in rates of death from any cause at 30 days (3.6% with nesiritide vs. 4.0% with placebo; absolute difference, -0.4 percentage points; 95% CI, -1.3 to 0.5) or rates of worsening renal function, defined by more than a 25% decrease in the estimated glomerular filtration rate (31.4% vs. 29.5%; odds ratio, 1.09; 95% CI, 0.98 to 1.21; P=0.11). CONCLUSIONS: Nesiritide was not associated with an increase or a decrease in the rate of death and rehospitalization and had a small, nonsignificant effect on dyspnea when used in combination with other therapies. It was not associated with a worsening of renal function, but it was associated with an increase in rates of hypotension. On the basis of these results, nesiritide cannot be recommended for routine use in the broad population of patients with acute heart failure. (Funded by Scios; ClinicalTrials.gov number, NCT00475852.).

The effect of recipient hepatitis C virus infection on outcomes following heart transplantation.

BACKGROUND: Insufficient data exist on the clinical course of hepatitis C virus (HCV) infection in heart transplant (HT) recipients. Our study reports the outcomes of heart transplantation in pretransplantation HCV-positive (HCV+) recipients. METHODS: A retrospective analysis of the heart transplantation database at our institution was performed to identify HT recipients who were HCV+ prior to transplantation. Chart reviews yielded demographic features, liver function tests, graft function, incidence of posttransplantation acute hepatitis and transplant coronary artery disease, and patient survival data. RESULTS: Between 1995 and 2006, 10 HCV+ patients underwent cardiac transplantation. The recipient mean age was 47 years (range, 23-69). Seven recipients were males and 3 were females. At listing 9 patients had no cirrhosis. One patient with Child-B cirrhosis was listed for combined heart-liver transplantation. Two of 10 donors were known to be HCV carriers. Posttransplantation in-hospital survival rate was 100%. At a mean follow-up of 58 months (range, 1.6-145), 3 deaths occurred, yielding an overall survival rate of 70%. Only 1 death (10%) was linked to accelerated acute hepatitis. Transplant coronary artery disease was detected in 2 patients (20%). Echocardiograms of survivors at last follow-up revealed normal ejection fractions. In addition, there were no cases of hepatocellular carcinoma; all survivors were without evidence of hepatic dysfunction. CONCLUSIONS: Transplanting recipients known to have HCV did not seem to affect overall posttransplantation survival or to increase the risk of liver dysfunction or graft-related complications.

Correlation of donor-specific antibodies, complement and its regulators with graft dysfunction in cardiac antibody-mediated rejection.

Antibody-mediated rejection (AMR) is an immunopathologic process in which activation of complement often results in allograft injury. This study correlates C4d and C3d with HLA serology and graft function as diagnostic criteria for AMR. Immunofluorescence staining for C4d and C3d was performed on 1511 biopsies from 330 patients as part of routine diagnostic work-up of rejection. Donor-specific antibodies were detected in 95% of those with C4d+C3d+ biopsies versus 35% in the C4d+C3d- group (p = 0.002). Allograft dysfunction was present in 84% in the C4d+ C3d+ group versus 5% in the C4d+C3d- group (p < 0.0001). Combined C4d and C3d positivity had a sensitivity of 100% and specificity of 99% for the pathologic diagnosis of AMR and a mortality of 37%. Since activation of complement does not always result in allograft dysfunction, we correlated the expression pattern of the complement regulators CD55 and CD59 in patients with and without complement deposition. The proportion of patients with CD55 and/or CD59 staining was highest in C4d+C3d- patients without allograft dysfunction (p = 0.03). We conclude that a panel of C4d and C3d is diagnostically more useful than C4d alone in the evaluation of AMR. CD55 and CD59 may play a protective role in patients with evidence of complement activation.

Post-transplant ischemic injury is associated with up-regulated AlloMap gene expression.

BACKGROUND: The AlloMap gene expression test is used for the non-invasive detection of rejection. However, the impact of early post-transplant ischemic injury on subsequent AlloMap gene expression analysis has not been evaluated before. METHODS: Sixty seven heart transplant recipients, mean age 53 years, were evaluated at a mean 34 months post-transplant. AlloMap score was determined on the same day of heart biopsies. Nineteen patients had evidence of early post-transplant ischemic injury (Injury group). These were compared with the remaining 48 patients, Control group. RESULTS: Using multiple regression model with a backward selection method, post-transplant ischemic injury was found to be associated with significant increased AlloMap score compared with controls (31.5 +/- 4.6 vs. 26 +/- 6.2, p < 0.001). The Injury group had increased transplant vasculopathy (KM 5-year freedom from vasculopathy: 34% vs. 52%, p = 0.015), than Controls. CONCLUSIONS: Post-transplant ischemic injury is associated with up-regulated AlloMap gene expression, and hence, may provide another explanation for a high score in the absence of rejection.

Attrition from heart transplant waiting list for patients on ventricular assist devices is not affected by desensitization strategies.

BACKGROUND: Ventricular assist device (VAD) patients, who are commonly sensitized, can be successfully transplanted using strategies aimed at diminishing antibody burden. However, the impact of these therapies on outcomes for VAD patients on the waiting list is ill-defined. The following study was conducted to ascertain the relationship between desensitization therapies and attrition rate from the waiting list for VAD patients. METHODS: The VAD patients listed between July 1996 and June 2002 were used for this report. Transplant and inpatient pharmacy databases were queried for demographics, date of transplantation, degree of allosensitization, use of desensitization therapy, immunosuppressive strategies, and specific causes of death. RESULTS: Among 232 patients listed for heart transplantation who required bridging to transplantation with a VAD, 79 (34%) died while on the waiting list. Common causes of death included multisystem organ failure in 32 (40.5%), sepsis in 19 (24.0%), and stroke in 10 (12.6%) patients. While nearly 50% of these patients were sensitized at listing, only 5 (6.3%) patients received desensitization therapy following VAD implantation. Therapies included mycophenolate mofetil in 3 (3.7%) and IVIG in 2 (2.5%) patients. Not a single patient underwent plasmapheresis or OKT3 therapy. CONCLUSION: For patients bridged to heart transplantation with a VAD, attrition from the waiting list was associated with factors other than desensitization or induction regimens.

Utility of long-term surveillance endomyocardial biopsy: a multi-institutional analysis.

BACKGROUND: The utility of long-term endomyocardial biopsy surveillance in heart transplant recipients has been questioned. This study was undertaken to identify risk factors for late rejection and to examine the impact of different biopsy surveillance protocols on outcomes using the registry of the Cardiac Transplant Research Database. METHODS: The study group consisted of all adult patients who underwent heart transplantation at the 33 centers participating in this investigation between January 1, 1993 and January 1, 2002, survived past the second post-transplant year, and were followed-up by a defined surveillance biopsy protocol. RESULTS: During a follow-up that consisted of 24,137 patient-years, 1,626 late rejections occurred. Shorter time since transplant, history of rejection, younger age and African-American ethnicity of the recipient were strong risk factors for late rejection. The practice of surveillance biopsy varied among institutions. Continued surveillance increased the rate of diagnosis of late rejection (RR = 1.3, p = 0.002). There was no reduction in the incidence of hemodynamically compromising rejection and no increase in survival in patients with long-term vs intermediate-term surveillance. Short-term surveillance was associated with an increased incidence of hemodynamically compromising rejection, particularly among high-risk patients, and increased mortality in African-American patients. CONCLUSIONS: There are no apparent benefits from surveillance biopsy beyond 5 years post-transplant. Surveillance biopsy between 2 and 5 years post-transplant was found to reduce mortality in African-American recipients. Non-African-American recipients at high risk for late rejection will likely benefit from surveillance up to 5 years post-transplant.

Noninvasive discrimination of rejection in cardiac allograft recipients using gene expression profiling.

Rejection diagnosis by endomyocardial biopsy (EMB) is invasive, expensive and variable. We investigated gene expression profiling of peripheral blood mononuclear cells (PBMC) to discriminate ISHLT grade 0 rejection (quiescence) from moderate/severe rejection (ISHLT > or = 3A). Patients were followed prospectively with blood sampling at post-transplant visits. Biopsies were graded by ISHLT criteria locally and by three independent pathologists blinded to clinical data. Known alloimmune pathways and leukocyte microarrays identified 252 candidate genes for which real-time PCR assays were developed. An 11 gene real-time PCR test was derived from a training set (n = 145 samples, 107 patients) using linear discriminant analysis (LDA), converted into a score (0-40), and validated prospectively in an independent set (n = 63 samples, 63 patients). The test distinguished biopsy-defined moderate/severe rejection from quiescence (p = 0.0018) in the validation set, and had agreement of 84% (95% CI 66% C94%) with grade ISHLT > or = 3A rejection. Patients >1 year post-transplant with scores below 30 (approximately 68% of the study population) are very unlikely to have grade > or = 3A rejection (NPV = 99.6%). Gene expression testing can detect absence of moderate/severe rejection, thus avoiding biopsy in certain clinical settings. Additional clinical experience is needed to establish the role of molecular testing for clinical event prediction and immunosuppression management.

Early and late rejection and HLA sensitization at the time of heart transplantation in patients bridged with left ventricular assist devices.

Over the years, the frequency of heart transplant candidates with HLA sensitization has increased as a result of the number of patients bridged to transplant using left ventricular assist devices (LVAD). Here we have examined 119 patients who were bridged to transplant with LVAD for a relationship between HLA antibodies and early (30 days) and late (2 years or more) rejection, as evidenced by endomyocardial biopsies. Both cytotoxic panel-reactive antibody reactions against a panel of T lymphocytes (T-PRA) and the percentage of transplants that occurred across a positive class I flow cross-match were examined. Biopsies were scored using ISHLT criteria. At 30 days, patients who had a biopsy grade of 0 had a mean T-PRA at transplant of 2.2%, while the mean PRAs of the other biopsy grades were significantly higher (P < .001). A similar pattern was seen with the highest biopsy results at 2 years or later (P < .001). None of the patients who had a grade 0 biopsy at 30 days posttransplant had a positive flow cytometry class I cross-match (P = .02), although the same pattern did not occur later due to a small number of patients (n = 3) who had negative biopsies. Thus, when biopsy results were examined early or late posttransplant, patients with negative biopsy results tended to have less HLA sensitization. While the methods of HLA sensitization involve humoral responses, more aggressive immunosuppression might be warranted to attempt to reduce cellular rejection posttransplant if HLA class I antibodies are present at the time of transplant.

Improving outcomes in heart transplantation: the potential of proliferation signal inhibitors.

Graft failure and mortality among heart transplant recipients remains higher than in populations receiving renal transplants. A major cause of graft loss is cardiac allograft vasculopathy (CAV), a condition characterized by diffuse thickening of coronary blood vessels. CAV often progresses silently, with major cardiac events (eg, ventricular arrhythmia) being the first presentation. Better diagnosis and monitoring of CAV is now possible with intravascular ultrasonography, a sensitive technique for measuring intimal thickness. To date, immunosuppressants have shown little efficacy for preventing CAV. However, a new class of agents, proliferation signal inhibitors (sirolimus and everolimus), have shown considerable efficacy in this regard and for preventing rejection. In an open-label trial, sirolimus therapy was associated with less intimal and medial proliferation than azathioprine. More robust evidence is available from a larger-scale, double-blind trial involving everolimus. At 12-month follow-up the incidence of CAV was significantly lower in patients receiving everolimus (35.7% and 30.4% for everolimus 1.5 and 3.0 mg/d vs 52.8% for azathioprine; P < .05). Sirolimus and everolimus were also associated with a lower rate of cytomegalovirus infection. As with other immunosuppressants, these agents are associated with adverse events (eg, hyperlipidemia), but they can be managed. Coadministration with calcineurin inhibitors (CNIs) can exacerbate CNI-related nephrotoxicity, but evidence suggests that everolimus administered with reduced-exposure cyclosporine in the maintenance phase preserves renal function without loss of immunosuppressive efficacy. Reduced CNI dosing in de novo patients is also a potential future benefit. Proliferation signal inhibitors have considerable potential for improving outcomes in heart transplantation.

B-type natriuretic peptide levels are not a surrogate marker for invasive hemodynamics during management of patients with severe heart failure.

BACKGROUND: We sought to assess the utility of serial BNP measurements in patients with severe heart failure and attempted to correlate values with invasively derived data. METHODS: In a retrospective study, we analyzed serial BNP levels in patients receiving hemodynamically guided therapy for severe heart failure and sought correlation with invasively derived data. RESULTS: Thirty-nine patients with New York Heart Association Class III-IV, with an ejection fraction of 35% or less, who had a pulmonary artery catheter inserted for hemodynamically tailored heart failure therapy, were identified and serial BNP measurements reviewed. BNP was estimated on admission, at 12 and 36 hours. Normally distributed variables are expressed as mean +/- SD and otherwise as median +/- interquartile range. Mean ejection fraction was 16% +/- 6%. Mean pulmonary artery occlusion pressures (PAOP) fell with therapy and were 25 +/- 7 mmHg, 18 +/- 7 mmHg and 19 +/- 7 mmHg at admission, 12 hours and 36 hours respectively ( P < 0.05). Median BNP levels fell from 1200 +/- 641 to 771 +/- 803 at 12 hours and to 805 +/- 771 at 36 hours (P < .001). There was no correlation between BNP and any hemodynamically derived variable. A change in BNP was not associated with a change in PAOP in any individual patient. Only 42% remained alive on medical therapy at 30 days. CONCLUSIONS: In patients with severe heart failure, BNP levels do not accurately predict serial hemodynamic changes and do not obviate the need for pulmonary artery catheterization.

Survival beyond 10 years following heart transplantation: The Cleveland Clinic Foundation experience.

BACKGROUND: Long-term survival after heart transplantation is a desirable although challenging goal. METHODS: We analyzed clinical outcomes in the cohort of 170 patients who have undergone heart transplantation at The Cleveland Clinic Foundation and survived >10 years. RESULTS: We found 10-year and 15-year survival rates of 54% and 41%, respectively, in these patients, but there was also a high incidence of complications, such as hypertension, renal dysfunction, transplant vasculopathy, and malignancy. CONCLUSIONS: Long-term survival following cardiac transplantation is possible although complications are frequent. Beyond 10 years, malignancy is a major cause of death.

Donor intracranial bleeding is associated with advanced transplant coronary vasculopathy: evidence from intravascular ultrasound.

OBJECTIVES: We evaluated the impact of spontaneous intracranial bleeding (ICB) in the donor on transplant coronary vasculopathy using serial intravascular ultrasound examinations. MATERIALS AND METHODS: Between January 1995 and December 2000, 72 recipients underwent cardiac transplantation from donors who had experienced spontaneous ICB (ICB group). Their findings using serial intravascular ultrasound analysis at baseline (within 1 month) and 1 year after transplantation were compared with 90 recipients who had undergone transplantation from trauma donors (trauma group). RESULTS: Compared with the Trauma group, the ICB group showed increased coronary intimal thickness (0.55 +/- 0.33 vs 0.39 +/- 0.3 mm; P = .034), plaque volume (3.84 +/- 2.5 vs 2.28 +/- 1.65 mm(3); P = .015) and plaque burden (7.4 vs 2%) at 1 year after transplantation. CONCLUSIONS: Donor spontaneous ICB is associated with significantly increased coronary vasculopathy.

Immunosuppression for cardiac transplantation--the past, present and future.

The field of cardiac transplant immunosuppression is rapidly developing and has evolved over the past 35 years. Anecdote, experience and registry based practice is giving way to an increasing bounty of well designed, randomized controlled trials which will guide future therapy. Current therapy is based on triple therapy with corticosteroids, a calcineurin inhibitor and an antimetabolite, but these regimens may be replaced by substitution or addition of newer antiproliferative agents. The true nemesis is coronary graft vasculopathy, which affects 50% of patients at 5 years and until recently had very few preventive therapeutic options. Renal toxicity remains among the most challenging adverse effects of immunosuppression to be overcome.

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.

Comparison of dobutamine-based and milrinone-based therapy for advanced decompensated congestive heart failure: Hemodynamic efficacy, clinical outcome, and economic impact.

BACKGROUND: The use of parenteral positive inotropic agents still remains a major component of therapy for patients with advanced decompensated congestive heart failure (CHF). However, no consensus guidelines have been developed for the appropriate selection of a first-line inotropic therapy. We sought to compare the clinical outcome and economic cost of dobutamine-based and milrinone-based therapy in patients with acute exacerbation of CHF. METHODS AND RESULTS: We retrospectively analyzed the outcome of 329 patients admitted to the heart failure unit with acute exacerbation of CHF. More patients were treated with dobutamine-based therapy (269/329, 81.7%) than with milrinone-based therapy (60/329, 18.3%). Both groups had similar baseline characteristics and similar hemodynamic profiles at baseline, with the exception of higher mean pulmonary arterial pressure in the milrinone group (47 mm Hg vs 42 mm Hg, P <.001). One hundred nine patients (40%) of the dobutamine group required parenteral nitroprusside for hemodynamic optimization compared with 11 patients (18%) in the milrinone group (P <.001). The use of parenteral nitroglycerin and dopamine was similar in both groups. There was no significant difference in the in-hospital mortality rate (dobutamine 7.8% vs milrinone 10%) or clinical outcome between the 2 groups. However, the average direct drug cost per patient was significantly reduced in the dobutamine group compared with the milrinone group ($45 +/- $10 vs $1855 +/- $350, P <.0001). CONCLUSION: Dobutamine-based therapy is an attractive approach for the treatment of decompensated advanced heart failure, achieving comparable clinical efficacy to milrinone with a significantly reduced economic cost.

Controlled trial of intravenous immune globulin in recent-onset dilated cardiomyopathy.

BACKGROUND: This prospective placebo-controlled trial was designed to determine whether intravenous immune globulin (IVIG) improves left ventricular ejection fraction (LVEF) in adults with recent onset of idiopathic dilated cardiomyopathy or myocarditis. METHODS AND RESULTS: Sixty-two patients (37 men, 25 women; mean age +/-SD 43.0+/-12.3 years) with recent onset (/=0.10 from study entry, and 20 (36%) of 56 normalized their ejection fraction (>/=0.50). The transplant-free survival rate was 92% at 1 year and 88% at 2 years. CONCLUSIONS: These results suggest that for patients with recent-onset dilated cardiomyopathy, IVIG does not augment the improvement in LVEF. However, in this overall cohort, LVEF improved significantly during follow-up, and the short-term prognosis remains favorable.

Partial left ventriculectomy for dilated cardiomyopathy: is this an alternative to transplantation?

OBJECTIVE: To determine the late effectiveness of partial left ventriculectomy and risk factors for failure. METHODS: Between May 1996 and December 1998, partial left ventriculectomy and concomitant mitral valve surgery were performed in 62 patients (95% transplant candidates) with a mean age of 54 years (range 17-72 years). All patients were in New York Heart Association functional class III (38%) or IV (62%) because of idiopathic dilated cardiomyopathy (59 patients) or ischemic, valvular, or familial cardiomyopathy (1 patient each). Outcomes considered for multivariable analysis included implantation of left ventricular assist device, return to class IV heart failure, relisting for transplantation, and death. RESULTS: Partial left ventriculectomy reduced the left ventricular end-diastolic diameter immediately preoperatively to immediately postoperatively (from 8.4 +/- 1.1 cm to 5.92 +/- 0.8 cm; P =.01), reduced the left ventricular end-diastolic volume index (from 133 +/- 48.6 mL to 64.1 +/- 26 mL; P <.0001), and increased the left ventricular ejection fraction (from 16 +/- 7.6 to 31.5 +/- 10.9; P <.0001). Survival was 80% and 60% at 1 and 3 years after surgery and freedom from failure was 49% and 26%, respectively. Increased systolic pulmonary artery pressure, decreased maximum exercise oxygen consumption, and increased left atrial pressure were associated with failure and/or death. The degree of preoperative mitral regurgitation did not correlate with clinical outcome. CONCLUSIONS: Early and late failures preclude the widespread use of partial left ventriculectomy. However, in view of its sometimes beneficial effect, use in situations that do not allow for transplantation or as a biologic bridge to transplantation may be appropriate.

Cellular rejection and rate of progression of transplant vasculopathy: a 3-year serial intravascular ultrasound study.

Intravascular ultrasound (IVUS) is established as the optimal method for early detection of transplant vasculopathy. The association between cellular rejection and development of transplant vasculopathy remains controversial. This study attempts to determine the rate of progression of transplant vasculopathy lesions and its relationship with cellular rejection in a long-term (> 1 year) IVUS serial follow-up.A study cohort of 47 patients undergoing heart transplantation from 1993 to 1995 was evaluated. Intravascular ultrasound was performed at baseline (within 8 weeks) and annually for a period of 3 years to determine maximum intimal thickness and maximum plaque area in each coronary segment. Significant allograft vasculopathy was defined as a site with intimal thickness > 0.5 mm not present at baseline. Biopsy results were scored by assigning a numerical weight to each ISHLT grade during the first year. Donor lesions ranged from 0.86 to 1.1 mm, showing no evidence of progression at serial follow-up. De novo lesions were identified in 30 patients. These lesions appeared yearly but progressed slowly. The average biopsy score in the entire cohort was 1.1 +/- 0.8. Average biopsy score was > 1.0 in 35 patients with significant linear correlation between the rate of intimal progression and biopsy score (r = 0.42, p = 0.01). Multivariate analysis demonstrated that only the biopsy score correlated with the rate of progression. Lesions of donor atherosclerosis do not change significantly after transplantation. However, de novo lesions continue to develop every year. In patients with evidence of rejection, the rate of progression of transplant vasculopathy correlates with the severity of rejection.