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Randall C Starling

Publications and source records attributed to Randall C Starling.

At least 19 recordsLinked to original sources
PubMed2006

Increased expression of angiotensin II type 1 receptor (AGTR1) in heart transplant recipients with recurrent rejection.

BACKGROUND: Angiotensin II receptor sub-type 1 (AGTR1) plays an important role in the regulation of the cellular immune process. We hypothesized that recurrent acute rejection is associated with increased gene expression of AGTR1 in human heart transplantation. METHODS: We identified a group of 14 heart transplant recipients who had recurrent acute cellular rejection (RAR), defined as three consecutive episodes of acute rejection (Grade > or =3A). These patients were matched to a control group (n = 15). mRNA gene expression of AGTR1 was measured in heart biopsy specimens of controls at 1 week post-transplant. AGTR1 mRNA was determined serially in the RAR group at baseline, each rejection episode, and after resolution of rejection. Angiotensin-converting enzyme (ACE) polymorphism was also evaluated. RESULTS: Both the control and RAR groups had similar mRNA AGTR1 expression at baseline. Compared with baseline, the RAR group had significantly increased mRNA expression of AGTR1 at the first episode of rejection (9-fold, p < 0.001), which increased further at the second episode (12-fold, p < 0.001) and peaked at the third episode (35-fold, p < 0.001). After resolution of rejection, AGTR1 expression was decreased significantly (p < 0.001), but remained elevated above baseline (6-fold, p < 0.001). No difference in ACE polymorphism was noted between the two groups. Compared with controls, the RAR patients had an increased incidence of hypertension, diabetes mellitus, chronic renal insufficiency and transplant vasculopathy during a mean follow-up period of 51.5 +/- 12 months. CONCLUSIONS: This is the first report to describe increased mRNA expression of AGTR1 in response to recurrent cellular rejection. Up-regulation of AGTR1 responds to treatment of rejection but not to complete recovery, a phenomenon that may potentially explain the link between rejection and subsequent clinical outcome.

Adult↗
PubMed2006

The impact of left ventricular reconstruction on survival in patients with ischemic cardiomyopathy.

OBJECTIVE: Left ventricular reconstruction (LVR) is performed to improve the morphologic structure and function of the heart in patients with heart failure. This procedure has been performed at the Cleveland Clinic Foundation since 1997. We assessed mortality, functional status, and predictors of outcome in these patients. METHODS: Data were extracted from multiple prospectively acquired datasets on demographic, clinical, and operative details of 220 consecutive patients who underwent LVR between July 1997 and July 2003, where the indication for surgery was heart failure (of whom 66% had New York Heart Association (NYHA) functional class III or IV symptoms). Mortality, functional status, and postoperative complications were ascertained by reference to the clinical record, social security death index, and by phone contact. Mean preoperative left ventricular ejection fraction (LVEF) was 21.5+/-7.3% and mean left ventricular end-diastolic diameter was 6.4+/-1.0 cm. The mean age was 61.4+/-9.0 years and 80% were male. The majority (86%) of patients underwent concomitant coronary artery bypass grafting and 49% underwent mitral valve surgery. RESULTS: Thirty-day mortality was 1% and survival at 1, 3, and 5 years was 92%, 90%, and 80%, respectively. Of the survivors for whom data on NYHA functional class were available, 85% were in NYHA functional class I or II. Mortality was predicted by reduced preoperative ejection fraction <20% (unadjusted hazard ratio 1.53, p = 0.02), body mass index < or = 24 kg/m2 (unadjusted hazard ratio 1.69, p = 0.01), QRS duration > or = 130 ms (unadjusted hazard ratio 1.66, p = 0.01) and the requirement for renal replacement therapy postoperatively (unadjusted hazard ratio 3.85, p < 0.01). Mean LVEF improved to 24.7+/-8.86% (p < 0.01) and left ventricular volumes were also significantly reduced. CONCLUSIONS: In selected patients with heart failure, LVR, in conjunction with revascularization and valve surgery, is associated with excellent survival, improved symptoms, and improved LVEF and left ventricular dimensions.

Aged↗
PubMed2006

Mitral valve surgery in heart failure: insights from the Acorn Clinical Trial.

OBJECTIVE: The study objective was to evaluate in a prospective, randomized, multicenter trial the safety and efficacy of mitral valve surgery with and without the CorCap cardiac support device (Acorn Cardiovascular, St Paul, Minn) in patients with New York Heart Association Class II to IV heart failure. BACKGROUND: Although mitral valve surgery has been performed successfully in patients with heart failure, the safety and long-term efficacy have not been established in a multicenter prospective trial. Cardiac support devices that reduce ventricular wall stress and promote beneficial reverse remodeling have been proposed as a new treatment option as a stand-alone procedure and as an adjunct to mitral valve surgery. METHODS: A subgroup of 193 patients were enrolled in the mitral valve repair or replacement stratum of the Acorn Clinical Trial; 102 patients were randomized to the mitral valve surgery alone group (control) and 91 patients were randomized to mitral valve surgery with implantation of the CorCap cardiac support device. Patients were followed for a median duration of 22.9 months. RESULTS: For the entire mitral valve surgery group, the 30-day operative mortality rate was only 1.6% at 30 days. Mitral surgery was associated with progressive reductions in left ventricle end-diastolic volume, left ventricle end-systolic volume, and left ventricular mass, and increases in left ventricle ejection fraction and sphericity index, all consistent with reverse remodeling. Recurrence of clinically significant mitral regurgitation was uncommon. Quality of life, exercise performance, and New York Heart Association functional class were all improved. Finally, the addition of the CorCap cardiac support device led to greater decreases in left ventricular end-diastolic volume and left ventricular end-systolic volume, a more elliptical shape, and a trend for a reduction in major cardiac procedures and improvement in quality of life compared with mitral surgery alone. CONCLUSIONS: These findings suggest that there is clear benefit to the surgical elimination of mitral regurgitation and that there is additional benefit with the CorCap cardiac support device. Given the improvement in left ventricle structure and function, along with a low mortality rate, physicians should strongly consider offering mitral valve surgery in combination with the CorCap cardiac support device to patients with heart failure who are on an optimal medical regimen.

Cardiac Surgical Procedures↗
PubMed2006

Multicenter retrospective analysis of cardiovascular risk factors affecting long-term outcome of de novo cardiac transplant recipients.

BACKGROUND: Previous risk factor studies in cardiac transplant patients have analyzed pre-transplant risk factors as they relate to outcomes. This study is the first in-depth multicenter assessment of ongoing post-transplant risk factors in heart transplant patients and their impact on 5-year outcomes. METHODS: We reviewed 280 heart transplant patients who survived > 1 year for the impact of post-transplant risk factors (hyperlipidemia, hypertension, diabetes, body mass index [BMI] and renal dysfunction: 8 to 18 possible measurements over 5 years) on outcomes, including death, cardiac allograft vasculopathy (CAV) and non-fatal major adverse cardiac events (NF-MACE). RESULTS: Upon multivariate Cox regression analysis, significant findings were high total-cholesterol for NF-MACE (relative risk [RR] = 4.34, confidence interval [CI] 1.35 to 13.98, p = 0.01), presence of diabetes for NF-MACE (RR = 3.96, CI 1.24 to 12.65, p = 0.02) and high serum creatinine for graft death (RR = 1.59, CI 1.35 to 1.87, p < 0.001). No covariates were found to be significant for CAV. Other significant risk factors by univariate Cox regression models with time-dependent covariates included BMI > or = 33 for graft death. CONCLUSIONS: Post-transplant risk factors of hypercholesterolemia and diabetes are associated with NF-MACE, whereas high serum creatinine and BMI > or = 33 are associated with graft death. Risk factor modification, including direct therapy to minimize risk factors, should be considered.

Adult↗
PubMed2006

The impact of hypogammaglobulinemia on infection outcome in patients undergoing ventricular assist device implantation.

BACKGROUND: Infection is a major comorbidity after ventricular assist device (VAD) placement. Defects in cellular immunity have been reported after VAD placement. However, to our knowledge, quantitative immunoglobulin G (IgG) level determination and the impact of hypogammaglobulinemia (HGG) on infections after VAD implantation have not been evaluated before. METHODS: A total of 76 patients (mean age, 53 years) underwent VAD implantation as a bridge to transplantation and had IgG levels determined as a baseline before transplantation. Patients were divided into 2 groups according to IgG level: Control Group (n = 56, IgG > or = 700 mg/dl) and HGG Group (n = 20, IgG < 700 mg/dl). Infection outcome during the VAD course and after transplantation was analyzed in relation to the IgG level. RESULTS: Baseline characteristics were similar in both groups. The incidence of bacteremia (14/20 [70%] vs 18/56 [32%], p = 0.0032) and major infection (19/20 [95%] vs 31/56 [56%], p = 0.0009) were significantly increased in the HGG Group compared with the Control Group. After transplantation, the episodes of rejection were similar in both groups and survival was similar. The HGG Group experienced more cytomegalovirus infections compared with the Control Group (9/20 [45%] vs 9/56 [16%], p = 0.009). CONCLUSIONS: VAD patients with HGG are at increased risk of infections. After transplantation, these patients also experience increased cytomegalovirus infections. A randomized preemptive IgG replacement trial may be warranted in the future to determine if this intervention will alleviate the risk of infection.

Adult↗
PubMed2006

Tissue synchronization imaging and optimal left ventricular pacing site in cardiac resynchronization therapy.

The optimal pacing site in cardiac resynchronization therapy (CRT) remains controversial. Tissue synchronization imaging is a novel echocardiographic technique that color-codes for areas of maximal delay in myocardial velocities. This study aimed to identify whether the left ventricular (LV) pacing lead position in CRT should be guided by a patient's area of maximal mechanical delay. Fifty-four patients with advanced heart failure were assessed echocardiographically before and 6 months after CRT. Response was analyzed according to the relation between the LV lead position and the area of maximal delay to peak velocity by tissue synchronization imaging in the first half of the ejection phase: group 1 (n = 22) had lead placement corresponding to the segment of maximal delay; group 2 (n = 13) had lead placement 1 segment adjacent; and group 3 (n = 19) had lead placement remote from this site. Evidence of LV reverse remodeling and improved systolic function was documented in group 1 (mean percentage decrease in end-systolic volume 23%) more than in group 2 (mean decrease 15%), and more than in group 3 (mean increase 8.9%, p <0.0001 compared with groups 1 and 2). In group 1, 16 of 22 patients had reverse remodeling (>15% decrease in end-systolic volume); reverse remodeling was seen in 7 of 13 patients in group 2 and 1 of 19 in group 3. The placing of the lead position proximal to the site of maximal delay by tissue synchronization imaging was correlated with reverse remodeling (r = 0.449, p = 001). Of 7 patients with delay confined to the septum and anterior wall only, none had evidence of reverse remodeling after CRT. In conclusion, pacing at the site of maximal mechanical delay was associated with reverse remodeling. Individually tailored LV lead positioning should be considered before CRT.

Adult↗
PubMed2006

Improved survival after acute myocardial infarction complicated by cardiogenic shock with circulatory support and transplantation: comparing aggressive intervention with conservative treatment.

BACKGROUND: The prognosis for patients with myocardial infarction has steadily improved, but remains poor for those developing cardiogenic shock. Utilization of re-vascularization, mechanical circulatory support and transplantation in these patients may improve survival. METHODS: We retrospectively analyzed the clinical outcome of 138 consecutive patients at the Cleveland Clinic from 1992 to 1998 who met the criteria for cardiogenic shock after acute myocardial infarction. All patients received intensive medical therapy and intra-aortic balloon pump support. Forty-three patients received intensive medical therapy (conservative group) and 95 patients were treated aggressively (aggressive group). The aggressive group comprised patients who were treated with percutaneous intervention/coronary artery bypass grafting (n = 77, re-vascularization group), and patients who received circulatory support/cardiac transplantation (n = 18). RESULTS: The baseline demographics and angiographic and hemodynamic features were comparable for the two groups. The in-hospital mortality rate was significantly reduced in the aggressive group compared with the conservative group (54% vs 81%, p = 0.002). The in-hospital mortality rate of the circulatory support/transplant group was markedly reduced compared with the conservative group (33% vs 81%, p < 0.001), and was also significantly lower than that of the re-vascularization group (33% vs 63%, p= 0.03). The aggressive group had a markedly improved 5-year survival compared with the conservative group (30% vs 6.2%, p = 0.003). CONCLUSIONS: These data suggest that an aggressive strategy, particularly left ventricular assist device support as a bridge to heart transplantation, may improve survival in post-myocardial infarction patients with cardiogenic shock.

Aged↗
PubMed2006

Ventricular assist devices and aggressive immunosuppression: looking beyond overall survival.

BACKGROUND: Patients bridged to heart transplantation with a ventricular assist device (VAD) developed coronary vasculopathy at the same rate as non-bridged patients despite having higher levels of pre-formed antibodies. We hypothesized that allosensitized VAD patients have higher levels of immunosuppression and thus different morbidity and causes of mortality. METHODS: Patients who received a transplant between January 1996 and May 2002 were separated into 2 groups based on the need for VAD support as a bridge to transplantation. Transplant and Inpatient Pharmacy Databases and charts were queried for date of transplantation, degree of allosensitization, use of desensitization therapy, immunosuppressive strategies, number of treated rejection episodes, and specific causes of death. RESULTS: This study investigated 238 patients (125 VAD patients, 113 non-VAD patients). VAD patients were more likely to be allosensitized than non-VAD patients (20% vs 5%, p < 0.01). OKT3 was given to 22% of VAD patients as anti-rejection prophylaxis and 14% received pre-transplant plasmapheresis. Non-VAD patients rarely were desensitized (2.6% of non-VAD patients). After transplantation, 68 VAD patients (54%) and 44 non-VAD patients (39%) had episodes of severe rejection requiring therapy. Episodes of rejection in VAD patients were commonly treated with steroids (90%), plasmapheresis (10%), and OKT3 (7%), and episodes of rejection in non-VAD patients were treated with steroids (76%) and OKT3 (8%). The 5-year survival for both groups was similar (90% and 86% respectively, p = 0.31). VAD patients commonly died of sepsis (75%), and non-VAD patients died of rejection (39%) and ischemic transplant cardiomyopathy (30%). CONCLUSION: When short-term outcomes between bridged and non-bridged heart transplant recipients were compared, overall survival was similar but causes of death differed. Findings in this study might aid in the post-operative management of patients bridged to transplantation with a VAD.

Aged↗
PubMed2006

Donor or recipient hepatitis B seropositivity is associated with allograft vasculopathy.

BACKGROUND: Increasing interest has focused on possible viral triggers of cardiac allograft vasculopathy. Although much interest has centered on cytomegalovirus, it has recently been noted that donor hepatitis C seropositivity is associated with risk for accelerated vasculopathy. The current study hypothesized that hepatitis B (HBV) might be associated with accelerated vasculopathy. METHODS: Sixty-six patients who received heart transplants between September 1998 and July 2000 were analyzed by intravascular ultrasound within 6 weeks and again at 12 months after transplantation. These patients were divided into 2 groups: the HBV Group (n = 13) in which either the donor or recipient was seropositive for hepatitis B core antibody (HBcAb), and a Control Group (n = 53) in which neither donor nor recipient was positive for HBcAb. RESULTS: Baseline characteristics of the 2 groups were similar. The HBV Group had significant increase in the change in average intimal area (1.59 +/- 1.4 vs 0.46 +/- 0.4 mm2, p = 0.01) per mm length of the vessel compared with controls. Allograft vasculopathy at 1 year (defined as largest maximal intimal thickness increase of > or =0.50 mm) occurred in 46% of the HBV group compared with 24% of the control group (p = 0.05). When measured as an average maximal intimal thickness increase of >0.30 mm, allograft vasculopathy at 1 year occurred in 31% of the HBV Group compared with 5% of Controls (p = 0.01). CONCLUSIONS: These preliminary results suggest that HBV seropositivity in donor or recipient may be associated with an increased risk for cardiac allograft vasculopathy.

Coronary Disease↗
PubMed2006

Duration of inotropic support after left ventricular assist device implantation: risk factors and impact on outcome.

OBJECTIVES: Because duration of inotropic support after left ventricular assist device implantation has been recognized as a surrogate for right ventricular dysfunction, we sought to (1) identify its preimplantation risk factors, particularly its association with preimplantation right ventricular dysfunction, and (2) assess its impact on clinical outcomes. METHODS: Between 1991 and 2002, left ventricular assist devices were implanted in 207 patients, exclusive of those receiving preoperative mechanical circulatory support, which precluded measuring right ventricular stroke work. Duration of inotropic support was analyzed as a continuous variable, truncated by death or transplantation, and in turn as a risk factor for these 2 events. RESULTS: Inotropic support decreased from 100% on the day of implantation to 57%, 33%, and 22% by days 7, 14, and 21. Its duration was strongly associated with lower preimplantation right ventricular stroke work index, older age, and nonischemic cardiomyopathy and was associated (P < .04) with higher mortality before transplantation but not with transition to transplantation. We identified no preimplantation risk factors for right ventricular assist device use because of its relatively infrequent use in this population (18 patients, only 4 of whom survived to transplantation). CONCLUSION: Duration of inotropic support after left ventricular assist device insertion is strongly correlated with low preimplantation right ventricular stroke work index. In turn, it was associated with reduced survival to transplantation. Thus, right ventricular stroke work measured before implantation might be useful in decision making for biventricular support, destination therapy, or total artificial heart.

Cardiomyopathies↗
PubMed2006

Risks and outcomes of acute kidney injury requiring dialysis after cardiac transplantation.

BACKGROUND: Risk factors for postoperative acute kidney injury (AKI) are well described in nontransplantation settings. Data regarding risks and consequences of AKI after cardiac transplantation are unclear. METHODS: We analyzed 756 cardiac transplant recipients between 1993 and 2004. The primary outcome is postoperative AKI requiring dialysis therapy. Secondary outcomes are hospital mortality and postoperative morbidities, including cardiac, neurological, and serious infection. Wilcoxon rank-sum, chi-square, or Fisher exact tests were used for univariable comparison. A bootstrap-bagging procedure (1,000 repetitions) and multivariable logistic analysis with multiple imputation were used for the final model. RESULTS: AKI frequency was 5.8% (44 of 756 patients). By means of univariable analysis, preoperative risk factors for AKI were diabetes, prior cardiac surgery, intra-aortic balloon pump use, albumin level, creatinine level, clinical severity score, and cold ischemia time. Intraoperative risk factors were cardiopulmonary bypass time and transfusion requirement. By means of multivariate analysis, serum creatinine level (odds ratio [OR], 2.7; 95% confidence interval [CI], 1.6 to 4.6), serum albumin level (OR, 0.34; 95% CI, 0.21 to 0.54), insulin-requiring diabetes (OR, 3.5; 95% CI, 1.4 to 9.0), and cardiopulmonary bypass time (OR, 1.29; 95% CI, 1.02 to 1.64) were independent predictors of postoperative AKI. The overall postoperative mortality rate was 4.2%; it was 50% in patients with AKI compared with 1.4% in patients without AKI. AKI was associated with greater frequencies of cardiac, neurological, and serious infection morbidities (43.2%, 18.2%, and 54.6% versus 5.5%, 2.3%, and 7.2%, respectively; P < 0.001). CONCLUSION: AKI is associated with significant morbidity and mortality after cardiac transplantation. Predictors of AKI can be used to risk-stratify patients to ameliorate further kidney injury and offer a survival benefit.

Acute Kidney Injury↗
PubMed2006

Effects of surgical ventricular restoration on left ventricular function: dynamic MR imaging.

PURPOSE: To retrospectively evaluate with dynamic magnetic resonance (MR) imaging the changes in global and regional left ventricular (LV) function after surgical ventricular restoration (SVR) performed in chronic ischemic heart disease patients with large nonaneurysmal or aneurysmal postmyocardial infarction zones. MATERIALS AND METHODS: The study was performed with institutional review board approval, and a waiver of individual informed consent was obtained. The study was HIPAA compliant. Patients (83 men, 22 women; mean age, 61 years +/- 9 [standard deviation]) were evaluated with MR imaging before and after SVR as follows: pre-SVR examination (n = 105; 25 days +/- 39 before SVR; median, 7 days; range, 1-189 days), early post-SVR examination (n = 95, 7 days +/- 3 after SVR), and late post-SVR (n = 35, 313 days +/- 158 after SVR). Cine MR imaging allowed calculation of ejection fraction and rate-corrected velocity of circumferential fiber shortening (Vcf(C)) for global LV functional evaluation, whereas tagged MR imaging (spatial modulation of magnetization with harmonic phase analysis) permitted assessment of regional circumferential strain (E(C)) with coronary distribution. Vcf(C) and E(C) were computed at both LV base- and mid-LV short-axis levels remote from the site of anteroapical SVR. RESULTS: Prior to SVR, LV dilatation and diminished global and regional LV function were observed. At early post-SVR examination, Vcf(C) had improved significantly but E(C) showed a worsening trend overall, although only E(C )of the right coronary artery at the mid-LV level worsened significantly. At late post-SVR examination, Vcf(C) values were improved when compared with pre-SVR values, although E(C) showed no statistically significant improvement. When compared with that at early post-SVR examination, however, E(C) showed significant improvement in two segments: left anterior descending artery and right coronary artery at mid-LV level. CONCLUSION: Although volume-based indexes of global LV function improve significantly after SVR, regional LV function did not improve significantly; there was evidence of continued LV remodeling after SVR.

Cardiac Surgical Procedures↗
PubMed2005

Peritransplant ischemic injury is associated with up-regulation of stromal cell-derived factor-1.

OBJECTIVES: We evaluated chimerism and stromal cell-derived factor-1 (SDF-1) expression in response to peritransplant ischemic injury following human heart transplantation. BACKGROUND: Myocardial ischemia has been shown to trigger mobilization of stem cells to the heart in animal experiments. METHODS: Between January 1998 and April 2002, a total of 114 male recipients received hearts from female donors. Of these 114 recipients, 26 had evidence of ischemic injury on their initial heart biopsies (ischemia group). These were compared to the remaining 88 patients (control group). Heart biopsy specimens obtained initially at one week and at one year after transplant were evaluated from 20 matched patients of each group for the presence of Y chromosome-containing nuclei. The SDF-1 messenger ribonucleic acid (mRNA) and protein expression were also evaluated on initial heart biopsy specimens. RESULTS: At one week, Y chromosome-containing nuclei were significantly increased in the ischemia group (0.68% vs. 0.04%; p < 0.0001) compared to the control group. These were positive for the stem cell factor receptor c-kit. A significant 3.3-fold increased mRNA expression (p = 0.001) and 2.8-fold increased protein expression (p = 0.01) of SDF-1 was noted in the ischemia group. At one year, Y chromosome was detected in 0.29% of cardiomyocyte nuclei in the ischemia group but none in the control group. The ischemia group had poorer survival and increased vasculopathy. CONCLUSIONS: This is the first report to describe chimerism and up-regulation of SDF-1 in human heart transplantation in response to ischemic injury.

Adult↗
PubMed2005

Usefulness of tissue doppler and color M-mode indexes of left ventricular diastolic function in predicting outcomes in systolic left ventricular heart failure (from the ADEPT study).

The prognostic values of tissue Doppler imaging and color M-mode diastolic indexes were studied in 225 patients who had symptomatic systolic heart failure in the ADEPT study. The primary end point of death, transplantation, or hospitalization due to heart failure occurred in 65 patients and was independently predicted by shorter deceleration time, lower ratio of pulmonary vein systolic to diastolic velocity, and increasing levels of the ratios of early transmitral velocity to early annular velocity or velocity of propagation. For the ratio of early transmitral velocity to early annular velocity, this prediction was additive to deceleration time. Newer diastolic indexes provide an independent prediction of clinical outcomes.

Age Factors↗
PubMed2005

Daclizumab to prevent rejection after cardiac transplantation.

BACKGROUND: Daclizumab, a humanized monoclonal antibody against the interleukin-2 receptor, reduced the risk of rejection without increasing the risk of infection among renal-transplant recipients and, in a single-center trial, among cardiac-transplant recipients. We conducted a multicenter, placebo-controlled, double-blind study to confirm these results in cardiac-transplant patients. METHODS: We randomly assigned 434 recipients of a first cardiac transplant treated with standard immunosuppression (cyclosporine, mycophenolate mofetil, and corticosteroids) to receive five doses of daclizumab or placebo. The primary end point was a composite of moderate or severe cellular rejection, hemodynamically significant graft dysfunction, a second transplantation, or death or loss to follow-up within six months. RESULTS: By six months, 104 of 218 patients in the placebo group had reached the primary end point, as compared with 77 of the 216 patients in the daclizumab group (47.7 percent vs. 35.6 percent, P=0.007), a 12.1 percent absolute risk reduction and a 25 percent relative reduction. The rate of rejection was lower in the daclizumab group than in the placebo group (41.3 percent vs. 25.5 percent). Among patients reaching the primary end point, the median time to the end point was almost three times as long in the daclizumab group as in the placebo group during the first 6 months (61 vs. 21 days) and at 1 year (96 vs. 26 days). More patients in the daclizumab group than in the placebo group died of infection (6 vs. 0) when they received concomitant cytolytic therapy. CONCLUSIONS: Daclizumab was efficacious as prophylaxis against acute cellular rejection after cardiac transplantation. Because of the excess risk of death, concurrent or anticipated use of cytolytic therapy with daclizumab should be avoided.

Adolescent↗
PubMed2005

Intravascular ultrasound evidence of angiographically silent progression in coronary atherosclerosis predicts long-term morbidity and mortality after cardiac transplantation.

OBJECTIVES: The aim of this study was to determine whether angiographically silent early coronary intimal thickening could predict long-term morbidity and mortality. BACKGROUND: Although intravascular ultrasound (IVUS) is widely used to detect early transplant coronary disease, its prognostic significance has not been well defined. METHODS: The study cohort consisted of 143 patients who underwent early multivessel (2.1 +/- 0.7 arteries/patient) IVUS examination 1.0 +/- 0.5 month and 12.0 +/- 1.0 month after transplantation. The change in intimal thickness was evaluated using paired analysis of 1,069 matched sites. Rapidly progressive vasculopathy was defined as the change in intimal thickness >/=0.5 mm. Patients were followed for a primary end point of all-cause mortality and a secondary composite end point of mortality and nonfatal myocardial infarction (MI). Angiographic disease, defined as any >/=50% diameter stenosis, was assessed in 126 patients. RESULTS: Intravascular ultrasound at one year demonstrated rapid progression in 54 (37%) of 143 patients and new lesions in 67 (47%) of 143 of patients. At a mean clinical follow-up of 5.9 years, more patients with rapidly progressive vasculopathy died, as compared with those without (26% vs. 11%, p = 0.03). Death and MI also occurred more frequently among those with rapid progression than in those without it (51% vs. 16%, p < 0.0001). There was no significant difference in outcome in patients with and without donor-transmitted lesions. Angiographic disease was found in 11 (22%) of 50 patients with and in 2 (2.1%) of 76 patients without (p = 0.003) rapidly progressive vasculopathy. The IVUS-defined rapid progression correlated highly with future development of angiographic disease (p = 0.0005). CONCLUSIONS: Rapidly progressive vasculopathy by IVUS, defined as an increase of >/=0.5 mm in intimal thickness within the first year after transplantation, is a powerful predictor of all-cause mortality, MI, and angiographic abnormalities. Accordingly, such patients may be candidates for more aggressive anti-atherosclerotic and/or immunosuppressive therapy.

Adult↗