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BACKGROUND Cardiac allograft vasculopathy (CAV) is a major complication after heart transplantation (HT). Uric acid (UA) may play a role in CAV due to its role in stimulating T-cell-mediated immunity. Sirolimus is associated with CAV attenuation through a number of mechanisms, including immune-mediated effects. We aimed to determine whether UA is an independent predictor of CAV and whether conversion to sirolimus as primary immunosuppression modulates UA levels. METHODS We retrospectively analyzed a cohort of 224 patients who underwent HT between 2004 and 2015 and had serial coronary intravascular ultrasound (IVUS) studies. Serum UA levels were measured at baseline and last follow-up IVUS in all participants. CAV progression was assessed by measuring the change in plaque volume (ΔPV) and plaque index (ratio of plaque volume to vessel volume [ΔPI]) between last follow-up and baseline IVUS after correction for time of follow-up. RESULTS Patients with high (≥7 mg/dl) compared with low ( 0.50 mm3/mm) (hazard ratio 2.2, 95% confidence interval 1.1 to 4.6; p = 0.037). Sirolimus resulted in decreased UA levels (5.8 ± 1.4 vs 5.2 ± 1.5; p = 0.002) and patients converted to sirolimus and had low UA levels had the least CAV progression (p < 0.001). After adjustment for potential confounders, change in UA level was also an independent predictor of CAV progression. CONCLUSIONS UA is an independent predictor of CAV after HT. Sirolimus is associated with decreased UA levels and may explain one of the mechanisms by which sirolimus attenuates CAV progression.

Cardiac allograft vasculopathy (CAV) is an accelerated form of coronary artery disease, and optical coherence tomography (OCT) provides detailed microstructural information. The current study was designed to test the hypothesis that markers of plaque vulnerability derived from OCT could predict CAV progression after heart transplantation (HTx).In 34 consecutive patients (median 3.1 years from HTx), intravascular ultrasound (IVUS) and OCT were performed in the left anterior descending artery (LAD) during routine annual coronary angiography. The presence of vulnerability markers, such as lipid pools, thin-cap fibroatheroma, macrophages and microchannels, was assessed in 100 consecutive frames of OCT in 20-mm segments of proximal LAD. The total number of appearances of vulnerable markers was defined as the vulnerability score (VS). Plaque volume (PV) was measured in the same study segment using IVUS at baseline and at 1-year follow-up, and the association between the baseline VS and the subsequent change in percent PV (PV / vessel volume × 100 [%PV]) was evaluated.Follow-up IVUS study was conducted after 12.5 ± 1.3 months. The mean VS was 59.9 ± 44.6. Compared with the initial %PV, the follow-up %PV increased in the study segment (25.6 ± 13.7% to 31.8 ± 17.5%, p0.001). The correlations between baseline VS and Δ%PV were significant in the study segment (r = 0.757, p0.001). On multivariable analysis, only the VS correlated significantly with Δ%PV.Our results demonstrate that the markers of plaque vulnerability in OCT can predict the progression of CAV. Therefore, in patients with HTx, OCT may aid in determining prognosis and guiding therapy related to CAV.

Background In this study we examined the impact of continuous-flow left ventricular assist device (CF-LVAD) support on proximal thoracic aorta dimensions. Methods Aortic root and ascending aorta diameter were measured from serial echocardiograms before and after CF-LVAD implantation in patients with ≥6 months of support, and correlated with the development of >mild aortic valve insufficiency (AI). Results Of 162 patients included, mean age was 58 ± 11 years and 128 (79%) were male. Seventy-nine (63%) were destination therapy patients. Mean aortic root and ascending aorta diameters at baseline, 1 month, 6 months, 12 months and long-term follow-up (mean 2.0 ± 1.4 years) were 3.5 ± 0.4, 3.5 ± 0.3, 3.9 ± 0.3, 3.9 ± 0.2 and 4.0 ± 0.3, and 3.3 ± 0.2, 3.3 ± 0.3, 3.6 ± 0.2, 3.6 ± 0.3 and 3.6 ± 0.3 cm, respectively. Only change in aortic root diameter from 1-month to 6-month follow-up reached statistical significance ( p = 0.03). Nine (6%) patients had accelerated proximal thoracic aorta expansion (>0.5 cm/year), occurring predominantly in the first 6 months after implantation. These patients were older and more likely to have hypertension and baseline proximal thoracic aorta dilation. Forty-five (28%) patients developed >mild AI at long-term follow-up, including 7 of 9 (78%) of those with accelerated proximal thoracic aorta expansion. All 7 had aortic valves that remained closed throughout the cardiac cycle, and this, along with duration of CF-LVAD support and increase in aortic root diameter, were significantly associated with developing >mild AI. Conclusion CF-LVAD patients have small increases in proximal thoracic aorta dimensions that predominantly occur within the first 6 months after implantation and then stabilize. Increasing aortic root diameter was associated with AI development.

Purpose For optimization of the pump setting, there is currently a lack of non-invasive diagnostic methods capable to sensitively reflect the altered right-to-left ventricle relationship following the Left Ventricle Assist Device (LVAD) implantation. It was hypothesized that novel measures derived from the re-breath diffusing lung capacity for carbon monoxide (DLCO) technique may become a viable alternative to invasive hemodynamic studies. The present pilot study demonstrates feasibility and quantification of dynamic pulmonary variables including lung blood flow (Q) in the face of a device derived and clinical data. Methods 6 patients with LVAD participated in the present study (tab 1). Oxygen consumption and DLCO with its components were assessed pre- and during 12-15 min of low intensity (0.3 Watts/kg) exercise on a semi-recumbent ergometer. At constant LVAD speed, nitric oxide analyzer and mass spectrometer connected to a subject via a mouthpiece were used. Results During exercise, each patient demonstrated different patterns and magnitude of alterations in respiratory gas exchange (fig 1A). Moreover, variability of alteration in DLCO measures among patients was more prominent after correction for Q (fig 2B). Conclusion Distinct inter-personal responses in DLCO components and respiratory gas exchange to low intensity exercise may indicate that the re-breath DLCO technique can be utilized for a non-invasive LVAD speed optimization.

Purpose Enhanced platelet reactivity may play a role in the development and progression of cardiac allograft vasculopathy (CAV). Although aspirin is often a part of the medication regimen after heart transplantation (HT), limited evidence is available on its effects on CAV and related outcomes. In this large study, we sought to investigate whether aspirin treatment has an independent impact on CAV progression using coronary intravascular ultrasound (IVUS) follow-up studies and clinical outcomes after long-term follow-up post HT. Methods CAV progression, all-cause and cardiac mortality were compared between HT patients taking and those not taking aspirin from 1994 to 2016 at a single institution. CAV progression was assessed by measuring the log ratio of the last to first plaque index (PI, ratio of plaque volume to vessel volume) between last follow-up and baseline coronary IVUS after adjustment for age, time to first IVUS, conversion to sirolimus, and time between IVUS studies. Survival analyses were performed using Cox regression models with aspirin treated as a time-dependent predictor conditional on patients being alive at 6 months post HT. Results Overall, 530 HT recipients (308 patients received sirolimus-based and 222 received calcineurin inhibitor-based immunosuppression) were retrospectively analyzed, among which 323 patients underwent at least 2 IVUS studies post HT. Length of aspirin use was modestly associated with attenuated progression of plaque index ratio (r=-0.14, p=0.02) (Figure 1A). Cox regression with adjustment for clinically relevant characteristics, including conversion to sirolimus, and CAV grade at 1 year post HT did not suggest any difference in all-cause mortality (hazard ratio [HR] 0.9; 95% confidence interval [CI] 0.6 to 1.3, p=0.45) (Figure 1B) or cardiac death (HR 1.5, 95% CI 0.7 to 3.2, p = 0.33) (Figure 1C) after a median follow-up time of 10 years post HT. Conclusion Aspirin use may delay CAV progression but does not affect long-term survival after HT.

Purpose Candidate selection for multi-organ transplants should consider the chances of good function and benefit of all transplanted organs. Risk factors for early renal graft dysfunction after combined heart-kidney transplant (CHKTx) may include vasoplegia and vasopressor need in spite of good cardiac graft function. We aimed to identify risk factors for vasoplegia after CHKTx and its impact on postoperative and renal allograft outcomes. Methods A retrospective review was conducted on 58 consecutive patients who underwent CHKTx at a single center between 1996 and 2019. Baseline characteristics, perioperative complications including post-transplant vasoplegia, graft function, and survival were assessed. Vasoplegia was defined as needing vasopressors to maintain a MAP >70 mmHg with either an ejection fraction >55% or a cardiac index ≥2.0 L/min/m2 within 48 hours of transplantation. Results The mean transplant age was 53.6 years (± 11.3 SD). Pre-transplant, 17 (29.3%) patients had a left ventricular assist device (VAD) and 1 (1.7%) had a right VAD. The operative mortality rate was 5.2% (3 patients). Seventeen (32.1%) patients experienced vasoplegia; of these, 10 (58.8%) had a VAD pre-transplant, 9 (52.9%) had delayed renal graft function (DGF), and 3 (17.6%) had permanent renal graft failure (PGF). All 3 patients with PGF had vasoplegia and 9 (50.0%) with DGF had vasoplegia. Eight (66.7%) of the patients with either DGF or PGF and vasoplegia had a VAD. Further survival analyses shown in table 1. Conclusion Vasoplegia is associated with a higher risk of renal allograft dysfunction following CHKTx, and is frequently associated with LVAD as a bridge to transplant. Identifying further risk factors associated with poor post-CHKTx renal graft function could help define patients for whom CHKTx is appropriate. A review of the CHKTx allocation process in high risk patient groups is warranted.

Purpose We hypothesized that self-management ability predicts quality of life (QOL) in heart transplant. Methods A multi-center, longitudinal survey of waitlisted heart transplant candidates was conducted. Structural equation modeling explored relationships among pre-transplant self-management ability scale (SMAS-30), emotional health, and physical health and post-transplant QOL. Emotional health was measured with validated instruments to measure resilience, uncertainty of illness, affect, and mood. Pre-transplant physical health was measured with Kansas City Cardiomyopathy Questionnaire subscales of physical limitation, symptom frequency, and symptom burden. We inspected the fit of the measurement model using guidelines indicative of desirable model fit: Comparative Fit Index (CFI)≥.95, Standardized Root Mean Square Residual (SRMSR) Results Participation rate was 48% (N=197). Median follow-up was 8 months (IQR 2.3 - 15.1) with 89 transplants, 22 deaths, and 24 delists. Post-transplant survey completion was 79%. Measurement model fit was excellent (CFI=.962; RMSEA=.057; SRMR=.06). Factor loadings were >.43 across factors. Pre-transplant self-management was highly correlated with emotional health (r=.81). Our hypothesized structural model had excellent fit (CFI=.962, RMSEA=.057; SRMR=.060). Self-management had a direct effect on emotional and physical health (r=.81 and r=.37, respectively). The direct path from self-management to QOL was not significant. However, indirect paths from self-management to post-transplant QOL with emotional or physical health as a mediator were significant (standardized coefficients=.29 and 0.10 with p=.015 and .005, respectively). Conclusion Increased self-management ability is associated with increased post-transplant QOL, mediated by pre-transplant emotional and pre-transplant physical health. Future attempts to improve QOL could target self-management ability.

Purpose Vasoplegia has been implicated in adverse outcomes after heart transplantation (HT). Although left ventricular assist device (LVAD) is associated with increased risk of vasoplegia, pre-operative predictors of vasoplegia in this population and its impact on survival after HT are unknown. In this study, we sought to examine predictors and outcomes of patients who develop vasoplegia after HT following bridging therapy with continuous flow LVAD. Methods We retrospectively analyzed 94 patients who underwent HT after bridging with LVAD between July, 2008 and June, 2018 at a large institution. Vasoplegia was defined as persistent low vascular resistance requiring ≥2 intravenous vasopressors within 48 hours post HT for >24 hours to maintain a mean arterial pressure >70 mm Hg. Logistic regression was used to examine predictors of vasoplegia and the association with survival was examined using Cox proportional hazard regression. Results Overall, 44 (46.8%) patients with LVAD developed vasoplegia after HT. Patients with and without vasoplegia had similar pre-operative LVAD, echocardiographic, and hemodynamic parameters. Patients with vasoplegia were significantly older, had longer LVAD support, higher pre-operative creatinine, cardiopulmonary bypass time (CBT), and Charlson comorbidity index, and had higher rates of hypothyroidism and sustained ventricular tachycardia (VT) (all p Conclusion Longer LVAD support, impaired renal function, sustained VT, and prolonged intra-operative CBT are independent predictors of vasoplegia in patients undergoing HT after LVAD bridging. Vasoplegia is associated with poor prognosis; hence, detailed assessment of these predictors can be clinically important.

Purpose Post-transplant malignancy is diagnosed in approximately 18% of heart transplant (HTx) recipients and is a leading long-term cause of death among these patients. The association between exposure to rabbit anti-thymocyte globulin (rATG), a polyclonal depleting antibody used for its immunomodulatory activity, and incidence of malignancy in HTx is unclear. Methods This is a single-center, retrospective chart review of all HTx recipients who received rATG induction between October 1, 2008 and December 31, 2015. ICD-9 codes were used to identify HTx patients who were diagnosed with any malignancy post-transplant (cases). A nested, case-control study design was used to determine the relative risk of rATG exposure with the incidence of malignancy post-transplant. Cancer cases were matched to controls in a 1:2 method based on age, sex, Epstein Barr Virus donor/recipient status, and year of transplant. Secondary analyses amongst 1:2 matches examined the impact of maintenance immunosuppression exposure on cancer risk using a weighted equation composed of the drug dose, duration, and trough values when applicable. Results Of the 126 patients included in the study, 25 developed malignancy. These 25 patient cases were matched to 50 control patients. The primary endpoint was to evaluate the association of rATG on the risk of malignancy. The median cumulative rATG dose in milligrams (mg) between groups was 365mg in cases and 465mg in controls (OR 0.94, 95% CI 0.79 - 1.11, p=0.46). The cumulative dose of rATG in mg/kg was 4.7 mg/kg in cases vs. 5.7 mg/kg in controls (OR 0.96, 95% CI 0.82 - 1.12, p=0.59). By both univariate and multivariate analyses, there were no statistically significant differences in malignancyassociated with the usage of or quantified exposure to tacrolimus, sirolimus, cyclosporine, or mycophenolate mofetil, although sirolimus showed anti-oncotic trends. Conclusion The results of this study demonstrate current rATG dosing strategies may not singularly be associated with malignancy development as previous dosing strategies suggested. Additional investigations are needed to explore the multiple factors associated with post-transplant malignancy as well as the possible modulating effect of sirolimus.

The purpose of this study was to analyze the post-hospital outcomes in patients with senile or familial cardiac amyloidosis treated with left ventricular assist device (LVAD) implantation. From December 1, 2008 to May 31, 2012, a total of 9 patients underwent LVAD placement for heart failure secondary to amyloidosis. Prior to LVAD placement, all patients were New York Heart Association (NYHA) Class IV and had a significantly decreased cardiac index (mean 1.93 liters/min/m(2) [1.64 to 2.36]). All patients tolerated LVAD implantation well. Post-operatively, 2 patients died prior to hospital discharge. Three patients died since discharge with a median survival of 13.7 months. Four patients remained alive with a follow-up of 16-24 months. The most common adverse event since placement has been gastrointestinal bleeding (3 of 9 patients). Firm conclusions cannot be drawn from our investigation, but the present observations suggest LVAD implantation is technically feasible for patients with severe heart failure due to advanced cardiac amyloidosis.

Background Exercise performance, an important aspect of quality of life, remains limited after heart transplantation (HTx). This study examines the effect of cardiac allograft remodeling on functional capacity after HTx. Methods The total cohort of 117 HTx recipients, based on echocardiographic determination of left ventricle mass and relative wall thickness at 1 year after HTx, was divided into 3 groups: (1) NG, normal geometry; (2) CR, concentric remodeling; and (3) CH, concentric hypertrophy. Cardiopulmonary exercise testing was performed 5.03 ± 3.08 years after HTx in all patients. Patients with acute rejection or significant graft vasculopathy were excluded. Results At 1 year post-HTx, 30% of patients had CH, 55% had CR and 15% had NG. Exercise tolerance, measured by maximum achieved metabolic equivalents (4.62 ± 1.44 vs 5.52 ± 0.96 kcal/kg/h), normalized peak Vo 2 (52 ± 14% vs 63 ± 12%) and Ve/Vco 2 (41 ± 17 vs 34 ± 6), was impaired in the CH group compared with the NG group. A peak Vo 2 ≤14 ml/kg/min was found in 6%, 22% and 48% of patients in the NG, CR and CH groups, respectively ( p = 0.01). The CH pattern was associated with a 7.4-fold increase in relative risk for a peak Vo 2 ≤14 ml/kg/min compared with NG patients (95% confidence interval 1.1 to 51.9, p = 0.001). After multivariate analysis, a 1-year CH pattern was independently associated with a reduced normalized peak Vo 2 ( p = 0.018) and an elevated Ve/Vco 2 ( p = 0.035). Conclusions The presence of CH at 1 year after HTx is independently associated with decreased normalized peak Vo 2 and increased ventilatory response in stable heart transplant recipients. The identification of CH, a potentially reversible mechanism of impairment in exercise capacity after HTx, may have major clinical implications.

The purpose of this study was to describe the normal values for strain (S), systolic strain rate (SRs) and synchrony by speckle-tracking echocardiography (STE) in heart transplant (HTx) recipients who had normal left ventricular ejection fraction (LVEF) and no clinically significant complications.We evaluated S and SRs in 40 HTx patients at 1 year after transplant and 82 healthy controls with STE using velocity vector imaging.Mean (SD) global longitudinal S and SRs, respectively, were lower in the transplant group compared with controls [-13.43% (2.39%) vs -17.28% (2.30%), p0.001; -0.83 (0.15) s(-1) vs -0.96 (0.13) s(-1), p0.001]. These variables were good for differentiating between groups: area under the curve was 0.88 for S and 0.73 for SRs. The differences remained significant after adjustment for other clinical variables. Global circumferential S and SRs were similar between groups. The standard deviation of the global longitudinal S time to peak of the 16 segments for HTx and control groups, respectively, was 41.67 (13.53) milliseconds vs 32.57 (12.81) milliseconds (p0.001). With 58.2 milliseconds as a cutoff value to define left ventricular synchrony, only 3 (8%) of the HTx patients and 4 (5%) of the control subjects were above that value (p = 0.6).To our knowledge, this is the first study describing normal values for S and SRs and synchrony by STE in a HTx population with normal LVEF: longitudinal S and SRs were reduced; circumferential deformation indexes were normal; and left ventricular synchrony was preserved.

Background Cardiac allograft vasculopathy (CAV) is primarily immune-mediated. We investigated the role of cellular rejection in CAV development. Methods The study comprised 252 cardiac transplant recipients (mean age, 49.02 ± 17.05 years; mean follow-up, 7.61 ± 4.49 years). Total rejection score (TRS) based on the 2004 International Society of Heart and Lung Transplantation R grading system (0R = 0, 1R=1, 2R=2, 3R=3) and any rejection score (ARS; calculated as 0R=0, 1R=1, 2R=1; 3R=1, or the number of rejections of any grade) were normalized for the total number of biopsy specimens. CAV was defined as coronary stenosis of 40% or more and/or distal pruning of secondary side branches. Thirty-two patients had undergone 3-dimensional intravascular ultrasound (IVUS) at baseline and with virtual histology (VH) IVUS at 24 months. Results In univariate analysis, 6-month TRS (hazard ratio [HR], 1.9; 95% confidence interval [CI], 0.99–3.90, p = 0.05) and ARS (HR, 2.22; 95% CI, 1.01–4.95; p = 0.047) were associated with increased risk of CAV. In multivariate analysis, 6-month TRS (HR, 2.84; 95% CI, 1.44–6.91, p = 0.02) was significantly associated with increased risk of CAV onset. The 12- and 24-month rejection scores were not risk factors for the onset of CAV. By Kaplan-Meier analysis, 6-month TRS exceeding 0.3 was associated with a significantly shorter time to CAV onset ( p = 0.018). There was direct correlation ( r = 0.44, p = 0.012) between TRS at 6 months and the percentage of necrotic core demonstrated by VH-IVUS at 24 months. Conclusion Recurrent cellular rejection has a cumulative effect on the onset of CAV. The mechanism may be due to increased inflammation resulting in increased plaque burden suggesting a relationship between the immune basis of cellular rejection and CAV.

Atrial rhythm disturbances, in particular atrial fibrillation (AF) and flutter (AFL), are common in the denervated transplanted heart. However, there is a relative paucity of data in the prevalence, mechanism of arrhythmia, and long-term significance.(1) Determine the prevalence of AF and AFL in heart transplant patients, (2) define the echo/Doppler features associated with arrhythmia, and (3) evaluate the impact of arrhythmia on long-term survival.All patients who received an orthotopic heart transplant at the Mayo Clinic, Rochester, Minnesota, between 1988 and 2000 were included. Analysis of serial electrocardiograms and Holter monitor records provided evidence of AF or AFL development. Variables including general patient demographics, histology-proven rejection numbers and grades, results of serial coronary angiography, endomyocardial biopsy specimens, and echocardiographic studies performed at 6 weeks and 3 years after transplant were obtained to determine variables predictive of arrhythmia development.There were 167 heart transplant recipients, of which 16 (9.5%) developed AF and another 25 (15.0%) developed AFL over 6.5 +/- 3.4 years. Patients who developed AF or AFL had lower left ventricular (LV) ejection fractions (56.6% +/- 1.6% vs 62.5% +/- 1.5%, p0.05), higher LV end-systolic dimensions (LVESD) (33.6 +/- 1.12 mm vs 29.7 +/- 0.97 mm, p0.01), higher right atrial volume indexes (43.2 +/- 12.3 ml vs 35 +/- 5.3 ml, p0.03), lower mitral deceleration time (145 +/- 8 msec vs 160 +/- 12 msec, p0.05), and lower late mitral annulus tissue a' velocities (0.06 +/- 0.005 cm/sec vs 0.08 +/- 0.01 cm/sec, p0.02) compared with an age- and gender-matched Sinus Rhythm Group. Grade 3 rejection was a time-dependent covariate predictor of AFL risk (hazard ratio [HR], 2.95; 95% confidence interval [CI], 1.3-6.6, p0.008) but not AF (HR, 2.264; 95% CI, 0.72-7.1; p = 0.10). Thirty-nine of 167 patients died: 13 in the arrhythmia group and 26 in the normal sinus rhythm group. Development of atrial dysrhythmia adversely affected the outcome in the first 5 years (p0.001) compared with normal sinus rhythm. Predictors of long-term mortality included AF/AFL (HR, 2.88; 95% CI, 1.38-5.96; p0.004), age at transplant (HR, 1.04; 95% CI, 1.00-1.07, p0.03), coronary artery disease (HR, 2.655; 95% CI, 1.25-5.64; p = 0.01), pre-transplant cardiac amyloidosis (HR, 5.02; 95% CI 2.37-10.62; p0.001), right atrial volume index (HR, 1.03; 95% CI, 1.00-10.7; p = 0.03), mitral deceleration time160 msec (p0.01), and LVESD30 mm (p0.04).Development of AF/AFL post-heart transplantation is not uncommon and is associated with decreased long-term survival. Cumulative effects of repeated moderate-to-severe (grade 3 or more) rejections that result in increased cardiac fibrosis are associated with the development of AFL, but not AF. Similarly advanced restrictive diastolic dysfunction caused by fibrosis from repeated moderate-to-severe (grade 3 or more) rejections was predominant in the patients with arrhythmia and was a marker of poor long-term outcome.

Background Cardiac allograft vasculopathy (CAV) is considered a major cause of morbidity and mortality in transplant recipients and may reflect immune-mediated endothelial injury in response to the donor heart. Elevated troponin levels in the donor serum might provide a marker for this phenomenon; therefore, we evaluated the relationship of donor troponin levels to the development of CAV. Methods A retrospective analysis of troponin levels was undertaken from cardiac donor patients, and transplant recipients were monitored for the development of vasculopathy by angiography (N = 171). Results Angiographically significant CAV developed in 6% of transplantation patients and troponin levels were inversely related to the severity of CAV. Conclusions Elevated donor troponin levels are not associated with the development of CAV but rather with a significantly reduced long-term risk of developing CAV, suggesting a possible protective effect of donor released protein.

Background: Tacrolimus (FK506) is a macrolide antibiotic that inhibits T-cell activation and proliferation. To date, all published trials have used tacrolimus and steroids in combination with either azathioprine or mycophenolate mofetil. Previous experience with pediatric cardiac transplant patients at our institution suggested that use of tacrolimus alone provides an adequate level of immunosuppression and that withdrawal of steroids is readily achieved in most recipients. Methods Between January 1, 1996, and July 7, 1999, we performed 77 adult cardiac transplants. Forty-three of these patients received tacrolimus and prednisone as primary immunosuppression, without azathioprine or mycophenolate mofetil. Thirty-two of the 43 patients started on tacrolimus have been weaned off steroids and are maintained on monotherapy. These latter patients form the basis of this report. Results The mean time for achieving monotherapy was 246 ± 127 days (range, 106 to 730). Grade ≥ 2 rejection occurred at 0.40 episodes per patient in the first 90 days (a combination of Grades 2 and 3A/3B rejections). The freedom from treated rejection (includes all 3A/3B and Grade 2 rejection in the first 90 days) was 69% at 90 days and 52% at 1 year. One patient (of 32) had documented cytomegalovirus infection (gastritis) diagnosed at 8 months post-transplant. We observed 1 case of transplant vasculopathy and 1 case of post-transplant lymphoproliferative disorder during the follow-up period. Conclusions Our results show that use of tacrolimus alone after steroid weaning provides effective immunosuppression with low incidence of rejection, cytomegalovirus infection, transplant arteriopathy, or post-transplant lymphoproliferative disease.

Purpose The Maze procedure is considered the definitive surgical approach to atrial fibrillation. Pulmonary hypertension (PH) has not been reported following Maze, but has been associated with radiofrequency ablation due to left atrial scarring and diastolic dysfunction (stiff left atrial syndrome). We sought to investigate the development of PH following Maze using echocardiographic indices. Methods and Materials Data from all patients undergoing Maze surgery between 1/1/1999 and 12/31/2004 at Mayo Clinic Rochester was retrospectively reviewed. Patients with adequate pre- and post-operative transthoracic echocardiograms (TTE) (>90 days after surgery) were included. Patients with congenital heart disease, isolated right-sided Maze, mitral stenosis, and pre-existing elevated right ventricular systolic pressure (RVSP ≥40 mm Hg) were excluded. Diastolic parameters including left atrial volume index, E/e’, and E:A were reported when available. Results Forty-one patients (26 males) met inclusion criteria. Mean age at surgery was 63 ± 10 years, with normal ejection fraction pre- and post-operatively (60 vs 58%). Two patients underwent Maze surgery only, 5 had coronary bypass grafting, 36 had concomitant valvular operations (29 mitral, 4 aortic, 3 tricuspid), and 2 underwent septal myectomy for hypertrophic obstructive cardiomyopathy. Median RVSP increased from 32 mm Hg (interquartile range [IQ] 27;37) pre-operatively to 41 mm Hg (IQ 33;58) post-operatively. RVSP ≥40 mm Hg was observed in 26/41 patients on 150 total post-operative TTEs at a median follow-up of 1545 days (IQ 610;2339). Measures of left ventricular diastolic function worsened, with median pre-operative E/e’ of 14 (IQ 10;18) increasing to 22 (IQ 15;28), and median E:A ratio increasing from 1.8 (IQ 1.1;2.4) to 2.33 (IQ 2.0;3.3). Conclusions Maze surgery may be complicated by the development of increased right heart pressures and worsening diastolic function, raising the possibility that stiff left atrial syndrome may be a significant sequela of Maze surgery warranting further study.